{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T13:31:18Z","timestamp":1767965478351,"version":"3.49.0"},"reference-count":113,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T00:00:00Z","timestamp":1679788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Laron syndrome (LS) is a rare genetic disorder characterized by low levels of insulin-like growth factor 1 (IGF1) and high levels of growth hormone (GH) due to mutations in the growth hormone receptor gene (GHR). A GHR-knockout (GHR-KO) pig was developed as a model for LS, which displays many of the same features as humans with LS-like transient juvenile hypoglycemia. This study aimed to investigate the effects of impaired GHR signaling on immune functions and immunometabolism in GHR-KO pigs. GHR are located on various cell types of the immune system. Therefore, we investigated lymphocyte subsets, proliferative and respiratory capacity of peripheral blood mononuclear cells (PBMCs), proteome profiles of CD4\u2212 and CD4+ lymphocytes and IFN-\u03b1 serum levels between wild-type (WT) controls and GHR-KO pigs, which revealed significant differences in the relative proportion of the CD4+CD8\u03b1\u2212 subpopulation and in IFN-\u03b1 levels. We detected no significant difference in the respiratory capacity and the capacity for polyclonal stimulation in PBMCs between the two groups. But proteome analysis of CD4+ and CD4\u2212 lymphocyte populations revealed multiple significant protein abundance differences between GHR-KO and WT pigs, involving pathways related to amino acid metabolism, beta-oxidation of fatty acids, insulin secretion signaling, and oxidative phosphorylation. This study highlights the potential use of GHR-KO pigs as a model for studying the effects of impaired GHR signaling on immune functions.<\/jats:p>","DOI":"10.3390\/biom13040597","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T03:31:48Z","timestamp":1679887908000},"page":"597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome"],"prefix":"10.3390","volume":"13","author":[{"given":"Marie-Christin","family":"Schilloks","sequence":"first","affiliation":[{"name":"Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella-Maria","family":"Giese","sequence":"additional","affiliation":[{"name":"Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arne","family":"Hinrichs","sequence":"additional","affiliation":[{"name":"Chair of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, D-85764 Oberschlei\u00dfheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Korbonits","sequence":"additional","affiliation":[{"name":"Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1630-6827","authenticated-orcid":false,"given":"Stefanie M.","family":"Hauck","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Core, Helmholtz Center Munich, German Research Center for Environmental Health, D-80939 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0430-9510","authenticated-orcid":false,"given":"Eckhard","family":"Wolf","sequence":"additional","affiliation":[{"name":"Chair of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, D-85764 Oberschlei\u00dfheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0375-3190","authenticated-orcid":false,"given":"Cornelia A.","family":"Deeg","sequence":"additional","affiliation":[{"name":"Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Werner, H., Sarfstein, R., Nagaraj, K., and Laron, Z. (2020). Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation. Cells, 9.","DOI":"10.3390\/cells9112446"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Werner, H., Lapkina-Gendler, L., Achlaug, L., Nagaraj, K., Somri, L., Yaron-Saminsky, D., Pasmanik-Chor, M., Sarfstein, R., Laron, Z., and Yakar, S. (2019). Genome-Wide Profiling of Laron Syndrome Patients Identifies Novel Cancer Protection Pathways. Cells, 8.","DOI":"10.3390\/cells8060596"},{"key":"ref_3","first-page":"59","article-title":"Insights from the clinical phenotype of subjects with Laron syndrome in Ecuador","volume":"22","author":"Bautista","year":"2020","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"111038","DOI":"10.1016\/j.mce.2020.111038","article-title":"Effect of growth hormone on insulin signaling","volume":"518","author":"Sharma","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8083","DOI":"10.1073\/pnas.86.20.8083","article-title":"Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism","volume":"86","author":"Godowski","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41434-022-00329-2","article-title":"Toward gene therapy of Laron syndrome","volume":"29","author":"Werner","year":"2022","journal-title":"Gene Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ghir.2008.12.001","article-title":"Expression, regulation and biological actions of growth hormone (GH) and ghrelin in the immune system","volume":"19","author":"Hattori","year":"2009","journal-title":"Growth Horm. IGF Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1515\/JPEM.1994.7.3.245","article-title":"Growth Hormone (GH) and the Immune System: Impaired Phagocytic Function in Children with Idiopathic GH Deficiency is Corrected by Treatment with Biosynthetic GH","volume":"7","author":"Manfredi","year":"1994","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1016\/0024-3205(87)90545-5","article-title":"Effects of human growth hormone on immune functions: In vitro studies on cells of normal and growth hormone-deficient children","volume":"41","author":"Rapaport","year":"1987","journal-title":"Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.vetimm.2005.09.001","article-title":"Peripheral T lymphocyte changes in neonatal piglets: Relationship with growth hormone (GH), prolactin (PRL) and cortisol changes","volume":"110","author":"Borghetti","year":"2006","journal-title":"Veter.-Immunol. Immunopathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0090-1229(88)90159-6","article-title":"Lymphocyte subset distribution and natural killer activity in growth hormone deficiency before and during short-term treatment with growth hormone releasing hormone","volume":"48","author":"Kiess","year":"1988","journal-title":"Clin. Immunol. Immunopathol."},{"key":"ref_12","first-page":"157","article-title":"Modulating effect of growth hormone (GH) on PHA-induced lymphocyte proliferation","volume":"12","author":"Bozzola","year":"1988","journal-title":"Thymus"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1210\/endo.138.5.5108","article-title":"Growth Hormone Stimulates the Proliferation of Activated Mouse T Lymphocytes1","volume":"138","author":"Coelho","year":"1997","journal-title":"Endocrinology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/BF00661904","article-title":"Modulation of lymphoproliferation by human growth hormone","volume":"140","author":"Kiess","year":"1983","journal-title":"Eur. J. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S0022-3476(86)80113-5","article-title":"Suppression of immune function in growth hormone-deficient children during treatment with human growth hormone","volume":"109","author":"Rapaport","year":"1986","journal-title":"J. Pediatr."},{"key":"ref_16","first-page":"33","article-title":"Does Endogenous Growth Hormone Influence Immune Function? Immunological Studies in Laron\u2019s Dwarfism","volume":"4","author":"Mancuso","year":"1991","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_17","first-page":"3383","article-title":"High-Dose Growth Hormone Does Not Affect Proinflammatory Cytokine (Tumor Necrosis Factor-\u03b1, Interleukin-6, and Interferon-\u03b3) Release from Activated Peripheral Blood Mononuclear Cells or after Minimal to Moderate Surgical Stress*","volume":"85","author":"Kolstad","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1203\/00006450-198503000-00009","article-title":"Humoral and Cell-Mediated Immunity in Growth Hormone-Deficient Children: Effect of Therapy with Human Growth Hormone","volume":"19","author":"Abbassi","year":"1985","journal-title":"Pediatr. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1182\/blood-2014-05-575308","article-title":"Growth hormone receptor signaling is dispensable for HSC function and aging","volume":"124","author":"Stewart","year":"2014","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00441-020-03206-9","article-title":"The pig as a model for immunology research","volume":"380","author":"Pabst","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11102-021-01191-y","article-title":"Mice with gene alterations in the GH and IGF family","volume":"25","author":"Qian","year":"2021","journal-title":"Pituitary"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.4049\/jimmunol.172.5.2731","article-title":"Of mice and not men: Differences between mouse and human immunology","volume":"172","author":"Mestas","year":"2004","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1210\/endo.140.7.6854","article-title":"Growth Hormone (GH) and Prolactin Receptors in Human Peripheral Blood Mononuclear Cells: Relation with Age and GH-Binding Protein*","volume":"140","author":"Bresson","year":"1999","journal-title":"Endocrinology"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Doeing, D.C., Borowicz, J.L., and Crockett, E.T. (2003). Gender dimorphism in differential peripheral blood leukocyte counts in mice using cardiac, tail, foot, and saphenous vein puncture methods. BMC Clin. Pathol., 3.","DOI":"10.1186\/1472-6890-3-3"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/S0929-6646(08)60017-0","article-title":"Revision in Reference Ranges of Peripheral Total Leukocyte Count and Differential Leukocyte Percentages Based on a Normal Serum C-Reactive Protein Level","volume":"106","author":"Huang","year":"2007","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S0368-1742(53)80036-6","article-title":"The differential leucocyte count in the normal pig","volume":"63","author":"Luke","year":"1953","journal-title":"J. Comp. Pathol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Karalyan, Z., Zakaryan, H., Arzumanyan, H., Sargsyan, K., Voskanyan, H., Hakobyan, L., Abroyan, L., Avetisyan, A., and Karalova, E. (2012). Pathology of porcine peripheral white blood cells during infection with African swine fever virus. BMC Veter.-Res., 8.","DOI":"10.1186\/1746-6148-8-18"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lunney, J.K., Van Goor, A., Walker, K.E., Hailstock, T., Franklin, J., and Dai, C. (2021). Importance of the pig as a human biomedical model. Sci. Transl. Med., 13.","DOI":"10.1126\/scitranslmed.abd5758"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.molmet.2018.03.006","article-title":"Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver","volume":"11","author":"Hinrichs","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"607473","DOI":"10.3389\/fimmu.2020.607473","article-title":"Chronic Hyperglycemia Drives Functional Impairment of Lymphocytes in Diabetic INSC94Y Transgenic Pigs","volume":"11","author":"Giese","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_31","first-page":"13940739","article-title":"Interplay between the Adaptive Immune System and Insulin Resistance in Weight Loss Induced by Bariatric Surgery","volume":"2019","author":"Gonzalez","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12979-020-00211-y","article-title":"T cell phenotypes associated with insulin resistance: Results from the Berlin Aging Study II","volume":"17","author":"Goldeck","year":"2020","journal-title":"Immun. Ageing"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.rvsc.2018.02.007","article-title":"Porcine cluster of differentiation (CD) markers 2018 update","volume":"118","author":"Dawson","year":"2018","journal-title":"Res. Veter.-Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1074\/mcp.M115.052183","article-title":"The Proteome of Native Adult M\u00fcller Glial Cells From Murine Retina","volume":"15","author":"Grosche","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Zougman","year":"2009","journal-title":"Nat. Methods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1021\/acs.jproteome.9b00580","article-title":"Systematic Comparison of Strategies for the Enrichment of Lysosomes by Data Independent Acquisition","volume":"19","author":"Singh","year":"2019","journal-title":"J. Proteome Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1021\/pr050300l","article-title":"Normalization Approaches for Removing Systematic Biases Associated with Mass Spectrometry and Label-Free Proteomics","volume":"5","author":"Callister","year":"2006","journal-title":"J. Proteome Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/nmeth.1584","article-title":"mProphet: Automated data processing and statistical validation for large-scale SRM experiments","volume":"8","author":"Reiter","year":"2011","journal-title":"Nat. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1038\/s41587-021-00968-7","article-title":"MaxDIA enables library-based and library-free data-independent acquisition proteomics","volume":"39","author":"Sinitcyn","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene-set enrichment tool for animals and plants","volume":"36","author":"Ge","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal analysis approaches in Ingenuity Pathway Analysis","volume":"30","author":"Green","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_42","first-page":"3","article-title":"Measuring Bioenergetics in T Cells Using a Seahorse Extracellular Flux Analyzer","volume":"113","author":"Chang","year":"2016","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"562","DOI":"10.2174\/1389201020666190528093432","article-title":"Mitogen-Induced Interferon Gamma Production in Human Whole Blood: The Effect of Heat and Cations","volume":"20","author":"Nam","year":"2019","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bekeredjian-Ding, I., Foermer, S., Kirschning, C.J., Parcina, M., and Heeg, K. (2012). Poke Weed Mitogen Requires Toll-Like Receptor Ligands for Proliferative Activity in Human and Murine B Lymphocytes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029806"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"396","DOI":"10.3389\/fimmu.2019.00396","article-title":"Expression of T-Bet, Eomesodermin, and GATA-3 Correlates With Distinct Phenotypes and Functional Properties in Porcine \u03b3\u03b4 T Cells","volume":"10","author":"Talker","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wang, P., Leng, X., Duan, J., Zhu, Y., Wang, J., Yan, Z., Min, S., Wei, D., and Wang, X. (2021). Functional Component Isolated from Phaseolus vulgaris Lectin Exerts In Vitro and In Vivo Anti-Tumor Activity through Potentiation of Apoptosis and Immunomodulation. Molecules, 26.","DOI":"10.3390\/molecules26020498"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3390\/immuno1030018","article-title":"Banana Lectin from Musa paradisiaca Is Mitogenic for Cow and Pig PBMC via IL-2 Pathway and ELF1","volume":"1","author":"Degroote","year":"2021","journal-title":"Immuno"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s00424-011-1039-x","article-title":"Differential pathways for calcium influx activated by concanavalin A and CD3 stimulation in Jurkat T cells","volume":"463","author":"Pang","year":"2011","journal-title":"Pflugers Arch."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1093\/glycob\/cwr182","article-title":"Control of mucin-type O-glycosylation: A classification of the polypeptide GalNAc-transferase gene family","volume":"22","author":"Bennett","year":"2011","journal-title":"Glycobiology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"24156","DOI":"10.1074\/jbc.270.41.24156","article-title":"Purification and cDNA Cloning of a Human UDP-N-acetyl-\u03b1- D-galactosamine:polypeptide N-Acetylgalactosaminyltransferase","volume":"270","author":"White","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/0925-4439(94)90025-6","article-title":"Structural organization and analysis of the human fumarylacetoacetate hydrolase gene in tyrosinemia type I","volume":"1226","author":"Awata","year":"1994","journal-title":"Biochim. Et Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zheng, Q., Wang, D., Lin, R., Lv, Q., and Wang, W. (2022). IFI44 is an immune evasion biomarker for SARS-CoV-2 and Staphylococcus aureus infection in patients with RA. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1013322"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"DeDiego, M.L., Nogales, A., Martinez-Sobrido, L., and Topham, D.J. (2019). Interferon-Induced Protein 44 Interacts with Cellular FK506-Binding Protein 5, Negatively Regulates Host Antiviral Responses, and Supports Virus Replication. Mbio, 10.","DOI":"10.1128\/mBio.01839-19"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1089\/jir.2007.0021","article-title":"Antiproliferative Activity of the Human IFN-\u03b1-Inducible Protein IFI44","volume":"27","author":"Hallen","year":"2007","journal-title":"J. Interf. Cytokine Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.dci.2017.07.006","article-title":"Characterizing porcine invariant natural killer T cells: A comparative study with NK cells and T cells","volume":"76","author":"Yang","year":"2017","journal-title":"Dev. Comp. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.3389\/fimmu.2017.01044","article-title":"Porcine B Cell Subset Responses to Toll-like Receptor Ligands","volume":"8","author":"Braun","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5595","DOI":"10.1210\/en.2003-0600","article-title":"Leptin Induces Growth Hormone Secretion from Peripheral Blood Mononuclear Cells via a Protein Kinase C- and Nitric Oxide-Dependent Mechanism","volume":"144","author":"Dixit","year":"2003","journal-title":"Endocrinology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.4049\/jimmunol.180.7.4476","article-title":"Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways","volume":"180","author":"Jacobs","year":"2008","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4670","DOI":"10.4049\/jimmunol.174.8.4670","article-title":"Glucose Availability Regulates IFN-\u03b3 Production and p70S6 Kinase Activation in CD8+ Effector T Cells","volume":"174","author":"Cham","year":"2005","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.vetimm.2007.06.022","article-title":"Cross-reactive anti-human monoclonal antibodies as a tool for B-cell identification in dogs and pigs","volume":"119","author":"Faldyna","year":"2007","journal-title":"Veter.-Immunol. Immunopathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1017\/S1466252307001235","article-title":"Biology of porcine T lymphocytes","volume":"7","author":"Charerntantanakul","year":"2006","journal-title":"Anim. Health Res. Rev."},{"key":"ref_62","first-page":"1003","article-title":"Advanced Onset of Puberty in Gilts of Thrifty genotype(Iberian Pig)","volume":"45","author":"Encinas","year":"2009","journal-title":"Reprod. Domest. Anim."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1159\/000071226","article-title":"Dose Effects of Growth Hormone during Puberty","volume":"60","author":"Saenger","year":"2003","journal-title":"Horm. Res. Paediatr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0165-2427(94)90120-1","article-title":"Porcine peripheral blood CD4+\/CD8+ dual expressing T-cells","volume":"43","author":"Pescovitz","year":"1994","journal-title":"Veter.-Immunol. Immunopathol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s12250-018-0073-7","article-title":"Phenotypic Characterization of Porcine IFN\u03b3-Producing Lymphocytes in Porcine Reproductive and Respiratory Syndrome Virus Vaccinated and Challenged Pigs","volume":"33","author":"Li","year":"2018","journal-title":"Virol. Sin."},{"key":"ref_66","first-page":"52","article-title":"Differences in the relative counts of peripheral blood lymphocyte subsets in various age groups of pigs","volume":"84","author":"Pietrasina","year":"2020","journal-title":"Can. J. Veter.-Res. = Rev. Can. Rech. Veter."},{"key":"ref_67","first-page":"500","article-title":"Functional and phenotypic analysis of porcine peripheral blood CD4\/CD8 double-positive T cells","volume":"87","author":"Zuckermann","year":"1996","journal-title":"Immunology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0165-2427(02)00002-8","article-title":"Blood lymphocyte subsets in pigs vaccinated and challenged with Actinobacillus pleuropneumoniae","volume":"86","author":"Appleyard","year":"2002","journal-title":"Veter.-Immunol. Immunopathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1354\/vp.40-4-395","article-title":"A Morphologic and Immunohistochemical Study of the Bronchus-associated Lymphoid Tissue of Pigs Naturally Infected with Mycoplasma hyopneumoniae","volume":"40","author":"Sarradell","year":"2003","journal-title":"Veter.-Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0008-8749(03)00172-2","article-title":"Differential requirements for proliferation of CD4+ and \u03b3\u03b4+ T cells to spirochetal antigens","volume":"224","author":"Hontecillas","year":"2003","journal-title":"Cell. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1099\/jmm.0.05359-0","article-title":"Differences in lymphocyte subpopulations and cell counts before and after experimentally induced swine dysentery","volume":"53","author":"Jonasson","year":"2004","journal-title":"J. Med. Microbiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e68","DOI":"10.1016\/j.rvsc.2010.11.005","article-title":"Evaluation of peripheral lymphocytes after weaning and vaccination for Mycoplasma hyopneumoniae","volume":"91","author":"Kick","year":"2011","journal-title":"Res. Veter.-Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0165-2427(02)00040-5","article-title":"Changes in the leucocyte subpopulations of the palatine tonsillar crypt epithelium of pigs in response to Streptococcus suis type 2 infection","volume":"87","author":"Salles","year":"2002","journal-title":"Veter.-Immunol. Immunopathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1016\/j.celrep.2016.01.044","article-title":"Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence","volume":"14","author":"Spadaro","year":"2016","journal-title":"Cell Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1046\/j.1365-2265.2002.01670.x","article-title":"Immune function during GH treatment in GH-deficient adults: An 18-month randomized, placebo-controlled, double-blinded trial","volume":"57","author":"Sneppen","year":"2002","journal-title":"Clin. Endocrinol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3389\/fendo.2018.00296","article-title":"The Severe Deficiency of the Somatotrope GH-Releasing Hormone\/Growth Hormone\/Insulin-Like Growth Factor 1 Axis of Ghrh\u2212\/\u2212 Mice Is Associated With an Important Splenic Atrophy and Relative B Lymphopenia","volume":"9","author":"Bodart","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"565","DOI":"10.3389\/fimmu.2017.00565","article-title":"Pathogen-Reactive T Helper Cell Analysis in the Pig","volume":"8","author":"Ebner","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.dci.2008.05.005","article-title":"The porcine dendritic cell family","volume":"33","author":"Summerfield","year":"2009","journal-title":"Dev. Comp. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Schupp, M., Chen, F., Briggs, E.R., Rao, S., Pelzmann, H.J., Pessentheiner, A.R., Bogner-Strauss, J.G., A Lazar, M., Baldwin, D., and Prokesch, A. (2013). Metabolite and transcriptome analysis during fasting suggest a role for the p53-Ddit4 axis in major metabolic tissues. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-758"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1007\/s00705-009-0460-3","article-title":"Activation and modulation of antiviral and apoptotic genes in pigs infected with classical swine fever viruses of high, moderate or low virulence","volume":"154","author":"Durand","year":"2009","journal-title":"Arch. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3389\/fnins.2019.00359","article-title":"Intermittent Fasting Exacerbates the Acute Immune and Behavioral Sickness Response to the Viral Mimic Poly(I:C) in Mice","volume":"13","author":"Zenz","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1089\/jir.2009.0085","article-title":"Association Between Capacity of Interferon-\u03b1 Production and Metabolic Parameters","volume":"30","author":"Tominaga","year":"2010","journal-title":"J. Interf. Cytokine Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1016\/j.cell.2018.10.001","article-title":"Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism","volume":"175","author":"Johnson","year":"2018","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.biocel.2006.12.002","article-title":"Expression of functional human glutaminase in baculovirus system: Affinity purification, kinetic and molecular characterization","volume":"39","author":"Lobo","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature12040","article-title":"Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway","volume":"496","author":"Son","year":"2013","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41577-019-0203-y","article-title":"Metabolic coordination of T cell quiescence and activation","volume":"20","author":"Chapman","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Xu, W., Patel, C.H., Zhao, L., Sun, I.-H., Oh, M.-H., Helms, R.S., Wen, J., and Powell, J.D. (2023). GOT1 regulates CD8+ effector and memory T cell generation. Cell Rep., 42.","DOI":"10.1016\/j.celrep.2022.111987"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"100978","DOI":"10.1016\/j.molmet.2020.100978","article-title":"Functional changes of the liver in the absence of growth hormone (GH) action \u2013 Proteomic and metabolomic insights from a GH receptor deficient pig model","volume":"36","author":"Riedel","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.7150\/ijbs.41051","article-title":"The Role of D-3-Phosphoglycerate Dehydrogenase in Cancer","volume":"16","author":"Zhao","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.cmet.2016.12.011","article-title":"Serine Is an Essential Metabolite for Effector T Cell Expansion","volume":"25","author":"Ma","year":"2017","journal-title":"Cell Metab."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"19952","DOI":"10.1074\/jbc.R117.819060","article-title":"Asparagine synthetase: Function, structure, and role in disease","volume":"292","author":"Lomelino","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Hope, H.C., Brownlie, R.J., Fife, C.M., Steele, L., Lorger, M., and Salmond, R.J. (2021). Coordination of asparagine uptake and asparagine synthetase expression modulates CD8+ T cell activation. J. Clin. Investig., 6.","DOI":"10.1172\/jci.insight.137761"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1016\/j.cell.2018.10.022","article-title":"Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression","volume":"175","author":"Schmiedel","year":"2018","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1042\/bj3120717","article-title":"Urea synthesis in enterocytes of developing pigs","volume":"312","author":"Wu","year":"1995","journal-title":"Biochem. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.cmet.2022.06.008","article-title":"Tumor cells dictate anti-tumor immune responses by altering pyruvate utilization and succinate signaling in CD8+ T cells","volume":"34","author":"Elia","year":"2022","journal-title":"Cell Metab."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1007\/s00125-008-1130-9","article-title":"The role of pyruvate carboxylase in insulin secretion and proliferation in rat pancreatic beta cells","volume":"51","author":"Xu","year":"2008","journal-title":"Diabetologia"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.immuni.2019.09.003","article-title":"Metabolic Profiling Using Stable Isotope Tracing Reveals Distinct Patterns of Glucose Utilization by Physiologically Activated CD8+ T Cells","volume":"51","author":"Ma","year":"2019","journal-title":"Immunity"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1038\/s41590-019-0495-x","article-title":"Quantitative analysis of T cell proteomes and environmental sensors during T cell differentiation","volume":"20","author":"Howden","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"6979","DOI":"10.1038\/s41467-021-27087-w","article-title":"A DAP5\/eIF3d alternate mRNA translation mechanism promotes differentiation and immune suppression by human regulatory T cells","volume":"12","author":"Volta","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1210\/er.2010-0009","article-title":"Endocrine Parameters and Phenotypes of the Growth Hormone Receptor Gene Disrupted (GHR\u2212\/\u2212) Mouse","volume":"32","author":"List","year":"2010","journal-title":"Endocr. Rev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/mt.2012.39","article-title":"Long-term Correction of Very Long-chain Acyl-CoA Dehydrogenase Deficiency in Mice Using AAV9 Gene Therapy","volume":"20","author":"Keeler","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"10496","DOI":"10.1073\/pnas.92.23.10496","article-title":"Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood","volume":"92","author":"Strauss","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_103","first-page":"273","article-title":"Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and molecular characterization of its deficiency in two patients","volume":"57","author":"Aoyama","year":"1995","journal-title":"Am. J. Hum. Genet."},{"key":"ref_104","first-page":"958","article-title":"Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: Diagnosis by acylcarnitine analysis in blood","volume":"52","author":"Zhang","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Manzo, T., Prentice, B.M., Anderson, K.G., Raman, A., Schalck, A., Codreanu, G.S., Lauson, C.B.N., Tiberti, S., Raimondi, A., and Jones, M.A. (2020). Accumulation of long-chain fatty acids in the tumor microenvironment drives dysfunction in intrapancreatic CD8+ T cells. J. Exp. Med., 217.","DOI":"10.1084\/jem.20191920"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.immuni.2007.07.008","article-title":"Revving the Engine: Signal Transduction Fuels T Cell Activation","volume":"27","author":"Jones","year":"2007","journal-title":"Immunity"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.2337\/db12-1219","article-title":"Methods for Assessing Mitochondrial Function in Diabetes","volume":"62","author":"Perry","year":"2013","journal-title":"Diabetes"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Haznadar, M. (2019). Cancer Metabolism: Methods and Protocols, Springer.","DOI":"10.1007\/978-1-4939-9027-6"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.12688\/f1000research.12802.2","article-title":"Monocytes isolated by positive and negative magnetic sorting techniques show different molecular characteristics and immunophenotypic behaviour","volume":"6","author":"Bhattacharjee","year":"2017","journal-title":"F1000Research"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1093\/intimm\/4.9.995","article-title":"Extensive CD4 cross-linking inhibits T cell activation by anti-receptor antibody but not by antigen","volume":"4","author":"Dianzani","year":"1992","journal-title":"Int. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/jlb.54.5.430","article-title":"Preincubation with anti-CD4 influences activation of human T cells by subsequent co-cross-linking of CD4 with CD3","volume":"54","author":"Tsygankov","year":"1993","journal-title":"J. Leukoc. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/s42255-019-0084-1","article-title":"Entry of glucose- and glutamine-derived carbons into the citric acid cycle supports early steps of HIV-1 infection in CD4 T cells","volume":"1","author":"Clerc","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_113","first-page":"E405","article-title":"Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice","volume":"287","author":"Liu","year":"2004","journal-title":"Am. J. Physiol. Metab."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/4\/597\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:03:33Z","timestamp":1760123013000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/4\/597"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,26]]},"references-count":113,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["biom13040597"],"URL":"https:\/\/doi.org\/10.3390\/biom13040597","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,26]]}}}