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This study aimed to investigate the effect of gastrointestinal (GI) nematode infection on host DNAm. Helminth-free Holstein steers were either infected with Ostertagia ostertagi (the brown stomach worm) or given tap water only as a control. Animals were euthanized 30 days post-infection, and tissues were collected at necropsy. We conducted epigenome-wide profiling using a mammalian methylation array to explore the impact of infection on methylation patterns in the mucosa from abomasal fundus (FUN), pylorus (PYL), draining lymph nodes (dLNs), and the duodenum (DUO). The analysis covered 31,107 cattle CpGs of 5082 genes and revealed infection-driven, tissue-specific, differential methylation patterns. A total of 389 shared and 2770 tissue-specific, differentially methylated positions (DMPs) were identified in dLN and FUN, particularly in genes associated with immune responses. The shared DMPs were found in 263 genes, many of which are involved in immune responses. Furthermore, 282, 244, 52, and 24 differentially methylated regions (DMRs) were observed in dLN, FUN, PYL, and DUO, respectively. More hypomethylated DMRs were detected in dLN and FUN, while more hypermethylated DMRs were found in PYL and DUO. Genes carrying DMPs and DMRs and enriched pathways relating to immune functions\/responses were detected in infected animals, indicating a link between DNA methylation and the infection. The data may implicate a crucial role of DNAm in regulating the nature\/strength of host immunity to infection and contribute to a deeper understanding of the epigenetic regulatory landscape in cattle infected by GI nematodes.<\/jats:p>","DOI":"10.3390\/ijms26010089","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T03:10:49Z","timestamp":1735182649000},"page":"89","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Profiling Genome-Wide Methylation Patterns in Cattle Infected with Ostertagia ostertagi"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6575-5266","authenticated-orcid":false,"given":"Clarissa","family":"Boschiero","sequence":"first","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705, USA"},{"name":"Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethiopia","family":"Beshah","sequence":"additional","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3764-8981","authenticated-orcid":false,"given":"Wenbin","family":"Tuo","sequence":"additional","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0192-6705","authenticated-orcid":false,"given":"George E.","family":"Liu","sequence":"additional","affiliation":[{"name":"Animal Genomics and Improvement Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1161\/CIRCULATIONAHA.110.956839","article-title":"Epigenetic modifications: Basic mechanisms and role in cardiovascular disease","volume":"123","author":"Handy","year":"2011","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhang, J., Sheng, H., Hu, C., Li, F., Cai, B., Ma, Y., Wang, Y., and Ma, Y. (2023). Effects of DNA Methylation on Gene Expression and Phenotypic Traits in Cattle: A Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241511882"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Li, E., and Zhang, Y. (2014). DNA methylation in mammals. Cold Spring Harb. Perspect. Biol., 6.","DOI":"10.1101\/cshperspect.a019133"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e176","DOI":"10.1093\/nar\/gni180","article-title":"Footprinting of mammalian promoters: Use of a CpG DNA methyltransferase revealing nucleosome positions at a single molecule level","volume":"33","author":"Fatemi","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kurdyukov, S., and Bullock, M. (2016). DNA Methylation Analysis: Choosing the Right Method. Biology, 5.","DOI":"10.3390\/biology5010003"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/s41467-022-28355-z","article-title":"A Mammalian Methylation Array for Profiling Methylation Levels at Conserved Sequences","volume":"13","author":"Arneson","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e2120887119","DOI":"10.1073\/pnas.2120887119","article-title":"DNA methylation clocks for dogs and humans","volume":"119","author":"Horvath","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1038\/s43587-023-00499-7","article-title":"Author Correction: Universal DNA methylation age across mammalian tissues","volume":"3","author":"Lu","year":"2023","journal-title":"Nat. Aging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e13349","DOI":"10.1111\/acel.13349","article-title":"Epigenetic clock and methylation study of oocytes from a bovine model of reproductive aging","volume":"20","author":"Kordowitzki","year":"2021","journal-title":"Aging Cell"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hu, Z., Boschiero, C., Li, C.J., Connor, E.E., Baldwin, R.L., and Liu, G.E. (2023). Unraveling the Genetic Basis of Feed Efficiency in Cattle through Integrated DNA Methylation and CattleGTEx Analysis. Genes, 14.","DOI":"10.3390\/genes14122121"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Caulton, A., Dodds, K.G., McRae, K.M., Couldrey, C., Horvath, S., and Clarke, S.M. (2021). Development of Epigenetic Clocks for Key Ruminant Species. Genes, 13.","DOI":"10.1101\/2021.06.30.450497"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Jhamat, N., Niazi, A., Guo, Y., Chanrot, M., Ivanova, E., Kelsey, G., Bongcam-Rudloff, E., Andersson, G., and Humblot, P. (2020). LPS-treatment of bovine endometrial epithelial cells causes differential DNA methylation of genes associated with inflammation and endometrial function. BMC Genom., 21.","DOI":"10.1186\/s12864-020-06777-7"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Usman, T., Ali, N., Wang, Y., and Yu, Y. (2021). Association of Aberrant DNA Methylation Level in the CD4 and JAK-STAT-Pathway-Related Genes with Mastitis Indicator Traits in Chinese Holstein Dairy Cattle. Animals, 12.","DOI":"10.3390\/ani12010065"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10689","DOI":"10.3168\/jds.2020-18404","article-title":"Short communication: Locus-specific interrelations between gene expression and DNA methylation patterns in bovine mammary gland infected by coagulase-positive and coagulase-negative staphylococci","volume":"103","author":"Zalewska","year":"2020","journal-title":"J. Dairy Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ribeiro, A.M.F., Sanglard, L.P., Wijesena, H.R., Ciobanu, D.C., Horvath, S., and Spangler, M.L. (2022). DNA methylation profile in beef cattle is influenced by additive genetics and age. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-16350-9"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1071\/RD17518","article-title":"Methylation of progesterone receptor isoform A and B promoters in the reproductive system of cows","volume":"30","author":"Rekawiecki","year":"2018","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, L., Hand, J.M., Fu, L., Smith, G.W., and Yao, J. (2019). DNA methylation and miRNA-1296 act in concert to mediate spatiotemporal expression of KPNA7 during bovine oocyte and early embryonic development. BMC Dev. Biol., 19.","DOI":"10.1186\/s12861-019-0204-x"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1262\/jrd.2020-137","article-title":"Differentially methylated CpG sites related to fertility in Japanese Black bull spermatozoa: Epigenetic biomarker candidates to predict sire conception rate","volume":"67","author":"Takeda","year":"2021","journal-title":"J. Reprod. Dev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Crouse, M.S., Caton, J.S., Claycombe-Larson, K.J., Diniz, W.J.S., Lindholm-Perry, A.K., Reynolds, L.P., Dahlen, C.R., Borowicz, P.P., and Ward, A.K. (2022). Epigenetic Modifier Supplementation Improves Mitochondrial Respiration and Growth Rates and Alters DNA Methylation of Bovine Embryonic Fibroblast Cells Cultured in Divergent Energy Supply. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.812764"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Salilew-Wondim, D., Saeed-Zidane, M., Hoelker, M., Gebremedhn, S., Poirier, M., Pandey, H.O., Tholen, E., Neuhoff, C., Held, E., and Besenfelder, U. (2018). Genome-wide DNA methylation patterns of bovine blastocysts derived from In Vivo embryos subjected to in vitro culture before, during or after embryonic genome activation. BMC Genom., 19.","DOI":"10.1186\/s12864-018-4826-3"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1080\/10495398.2021.1886944","article-title":"DNA methylation status of SERPINA3 gene involved in mRNA expression in three cattle breeds","volume":"33","author":"Wang","year":"2022","journal-title":"Anim. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Del Corvo, M., Lazzari, B., Capra, E., Zavarez, L., Milanesi, M., Utsunomiya, Y.T., Utsunomiya, A.T.H., Stella, A., de Paula Nogueira, G., and Garcia, J.F. (2021). Methylome Patterns of Cattle Adaptation to Heat Stress. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.633132"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tran Van Nhieu, G., and Arbibe, L. (2009). Genetic reprogramming of host cells by bacterial pathogens. F1000 Biol. Rep., 1.","DOI":"10.3410\/B1-80"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"de Soutello, R.V.G., Rodrigues, M.G.F., Gon\u00e7alves, J.A., Bello, H.J.S., Pavan, B.E., and Ramos, E.S. (2022). Global genomic methylation related to the degree of parasitism in cattle. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22753-5"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"giaa021","DOI":"10.1093\/gigascience\/giaa021","article-title":"De novo assembly of the cattle reference genome with single-molecule sequencing","volume":"9","author":"Rosen","year":"2020","journal-title":"GigaScience"},{"key":"ref_26","first-page":"e123","article-title":"SeSAMe: Reducing artifactual detection of DNA methylation by Infinium BeadChips in genomic deletions","volume":"46","author":"Zhou","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13072-019-0321-6","article-title":"MethylToSNP: Identifying SNPs in Illumina DNA methylation array data","volume":"12","author":"LaBarre","year":"2019","journal-title":"Epigenetics Chromatin"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0065-2776(07)96002-2","article-title":"Regulation of interferon-gamma during innate and adaptive immune responses","volume":"96","author":"Schoenborn","year":"2007","journal-title":"Adv. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1500637","DOI":"10.1126\/sciadv.1500637","article-title":"Neuron-specific SALM5 limits inflammation in the CNS via its interaction with HVEM","volume":"2","author":"Zhu","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ghanatsaman, Z.A., Mehrgardi, A.A., Nanaei, H.A., and Esmailizadeh, A. (2023). Comparative genomic analysis uncovers candidate genes related with milk production and adaptive traits in goat breeds. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-35973-0"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, M.D., Dzama, K., Hefer, C.A., and Muchadeyi, F.C. (2015). Genomic population structure and prevalence of copy number variations in South African Nguni cattle. BMC Genom., 16.","DOI":"10.1186\/s12864-015-2122-z"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.4049\/jimmunol.1600293","article-title":"Correction: SATB1 Plays a Critical Role in Establishment of Immune Tolerance","volume":"196","author":"Kondo","year":"2016","journal-title":"J. Iimmunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6954","DOI":"10.1038\/s41467-022-34345-y","article-title":"The 3D enhancer network of the developing T cell genome is shaped by SATB1","volume":"13","author":"Zelenka","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7111","DOI":"10.4049\/jimmunol.174.11.7111","article-title":"Transcription factor Tfec contributes to the IL-4-inducible expression of a small group of genes in mouse macrophages including the granulocyte colony-stimulating factor receptor","volume":"174","author":"Rehli","year":"2005","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.it.2019.03.001","article-title":"ZEBs: Novel Players in Immune Cell Development and Function","volume":"40","author":"Scott","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/\u03b2-catenin signalling: Function, biological mechanisms, and therapeutic opportunities","volume":"7","author":"Liu","year":"2022","journal-title":"Signal Transduct Target. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1186\/s13071-016-1770-4","article-title":"Wnt signaling in regulation of biological functions of the nurse cell harboring Trichinella spp.","volume":"9","author":"Dabrowska","year":"2016","journal-title":"Parasit. Vectors"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Oudhoff, M.J., Antignano, F., Chenery, A.L., Burrows, K., Redpath, S.A., Braam, M.J., Perona-Wright, G., and Zaph, C. (2016). Intestinal Epithelial Cell-Intrinsic Deletion of Setd7 Identifies Role for Developmental Pathways in Immunity to Helminth Infection. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005876"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1007\/s40495-017-0114-1","article-title":"Type 2 cytokine responses: Regulating immunity to helminth parasites and allergic inflammation","volume":"3","author":"Henry","year":"2017","journal-title":"Curr. Pharmacol. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1146\/annurev.immunol.15.1.505","article-title":"Cytokine regulation of host defense against parasitic gastrointestinal nematodes: Lessons from studies with rodent models","volume":"15","author":"Finkelman","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.1242\/jcs.030627","article-title":"Involvement of endothelial ephrin-B2 in adhesion and transmigration of EphB-receptor-expressing monocytes","volume":"121","author":"Pfaff","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/hep.27792","article-title":"The receptor tyrosine kinase EphB2 promotes hepatic fibrosis in mice","volume":"62","author":"Mimche","year":"2015","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"256","DOI":"10.5114\/pdia.2014.40954","article-title":"Interleukin-17 in human inflammatory diseases","volume":"31","author":"Shabgah","year":"2014","journal-title":"Postepy Dermatol. Alergol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bastid, J., Dejou, C., Docquier, A., and Bonnefoy, N. (2020). The Emerging Role of the IL-17B\/IL-17RB Pathway in Cancer. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00718"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1073\/pnas.97.2.773","article-title":"Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 cytokine family","volume":"97","author":"Li","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s12026-014-8545-9","article-title":"From inception to output, Tcf1 and Lef1 safeguard development of T cells and innate immune cells","volume":"59","author":"Steinke","year":"2014","journal-title":"Immunol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s13258-017-0635-3","article-title":"Selected microRNA-192 mutant indicates association with several function genes in bovine cells","volume":"40","author":"Zi","year":"2018","journal-title":"Genes Genom."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.isci.2019.07.039","article-title":"TMEM88 Inhibits Wnt Signaling by Promoting Wnt Signalosome Localization to Multivesicular Bodies","volume":"19","author":"Lee","year":"2019","journal-title":"iScience"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"11064","DOI":"10.1111\/jcmm.15755","article-title":"SATB2 is a novel biomarker and therapeutic target for cancer","volume":"24","author":"Roy","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lai, L.Y.S., Gracie, N.P., Gowripalan, A., Howell, L.M., and Newsome, T.P. (2022). SMAD proteins: Mediators of diverse outcomes during infection. Eur. J. Cell. Biol., 101.","DOI":"10.1016\/j.ejcb.2022.151204"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/imm.12076","article-title":"SMAD regulatory networks construct a balanced immune system","volume":"139","author":"Malhotra","year":"2013","journal-title":"Immunology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1111\/jcmm.13115","article-title":"Chinese 1 strain of Toxoplasma gondii excreted-secreted antigens negatively modulate Foxp3 via inhibition of the TGF\u00dfRII\/Smad2\/Smad3\/Smad4 pathway","volume":"21","author":"Chen","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.immuni.2014.12.019","article-title":"A critical role for transcription factor Smad4 in T cell function that is independent of transforming growth factor \u03b2 receptor signaling","volume":"42","author":"Gu","year":"2015","journal-title":"Immunity"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Yu, G., Chen, Y., Hu, Y., Zhou, Y., Ding, X., and Zhou, X. (2022). Roles of transducin-like enhancer of split (TLE) family proteins in tumorigenesis and immune regulation. Front. Cell. Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1010639"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1128\/MCB.00902-13","article-title":"Tle4 regulates epigenetic silencing of gamma interferon expression during effector T helper cell tolerance","volume":"34","author":"Bandyopadhyay","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"205","DOI":"10.5114\/ceji.2017.69363","article-title":"Early growth response 2 and Egr3 are unique regulators in immune system","volume":"42","author":"Taefehshokr","year":"2017","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hao, W., Wang, L., and Li, S. (2020). FKBP5 Regulates RIG-I-Mediated NF-\u03baB Activation and Influenza A Virus Infection. Viruses, 12.","DOI":"10.3390\/v12060672"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.tem.2011.08.001","article-title":"FKBP51 and FKBP52 in signaling and disease","volume":"22","author":"Storer","year":"2011","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12711-016-0197-x","article-title":"A genome-wide association study for genetic susceptibility to Mycobacterium bovis infection in dairy cattle identifies a susceptibility QTL on chromosome 23","volume":"48","author":"Richardson","year":"2016","journal-title":"Genet. Sel. Evol."},{"key":"ref_60","first-page":"567","article-title":"fosB is a transforming gene encoding a transcriptional activator","volume":"6","author":"Schuermann","year":"1991","journal-title":"Oncogene"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.fsi.2020.06.061","article-title":"Bacillus subtilis H2 modulates immune response, fat metabolism and bacterial flora in the gut of grass carp (Ctenopharyngodon idellus)","volume":"106","author":"Shi","year":"2020","journal-title":"Fish Shellfish Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1007\/s00262-022-03188-3","article-title":"OIT3 mediates macrophage polarization and facilitates hepatocellular carcinoma progression","volume":"71","author":"Yang","year":"2022","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1016\/j.immuni.2023.07.017","article-title":"A regulatory circuit controlled by extranuclear and nuclear retinoic acid receptor \u03b1 determines T cell activation and function","volume":"56","author":"Larange","year":"2023","journal-title":"Immunity"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e70051","DOI":"10.1002\/iid3.70051","article-title":"Retinoic Acid (RA): A Critical Immunoregulatory Molecule in Asthma and Allergies","volume":"12","author":"Lotfi","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1007\/s10875-013-9936-8","article-title":"The retinoic acid receptor agonist Am80 increases mucosal inflammation in an IL-6 dependent manner during Trichuris muris infection","volume":"33","author":"Hurst","year":"2013","journal-title":"J. Clin. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Minnone, G., De Benedetti, F., and Bracci-Laudiero, L. (2017). NGF and Its Receptors in the Regulation of Inflammatory Response. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18051028"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1084\/jem.20121846","article-title":"Bcl11a is essential for lymphoid development and negatively regulates p53","volume":"209","author":"Yu","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.cell.2015.10.013","article-title":"Fezf2 Orchestrates a Thymic Program of Self-Antigen Expression for Immune Tolerance","volume":"163","author":"Takaba","year":"2015","journal-title":"Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"18304","DOI":"10.1074\/jbc.M115.638064","article-title":"Nuclear Receptor Nr4a2 Promotes Alternative Polarization of Macrophages and Confers Protection in Sepsis","volume":"290","author":"Mahajan","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nrc2826","article-title":"The Hox genes and their roles in oncogenesis","volume":"10","author":"Shah","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1097\/00001756-199405000-00003","article-title":"Schistosoma mansoni infection enhances the levels of NGF in the liver and hypothalamus of mice","volume":"5","author":"Aloe","year":"1994","journal-title":"Neuroreport"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1007\/s004010050522","article-title":"Chronic parasite infection in mice induces brain granulomas and differentially alters brain nerve growth factor levels and thermal responses in paws","volume":"92","author":"Aloe","year":"1996","journal-title":"Acta Neuropathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.micinf.2011.10.006","article-title":"The role of interleukin-15 in inflammation and immune responses to infection: Implications for its therapeutic use","volume":"14","author":"Perera","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Yu, Y., Zhang, P., Ma, G., Zhang, M., Liang, Y., Jiao, W., and Niu, H. (2021). Identification of NTRK3 as a potential prognostic biomarker associated with tumor mutation burden and immune infiltration in bladder cancer. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08229-1"},{"key":"ref_75","unstructured":"Boschiero, C., Beshah, E., Bakshi, M., Thompson, P., Zhu, X., Liu, G.E., and Tuo, W. (2024). Time-dependent RNA transcriptional profiling of abomasal mucosa in cattle infected with Ostertagia ostertagi, Submitted."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.immuni.2017.12.012","article-title":"Regulation of the Immune Response by the Aryl Hydrocarbon Receptor","volume":"48","author":"Quintana","year":"2018","journal-title":"Immunity"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Chen, Y., Wang, Y., Fu, Y., Yin, Y., and Xu, K. (2023). Modulating AHR function offers exciting therapeutic potential in gut immunity and inflammation. Cell Biosci., 13.","DOI":"10.1186\/s13578-023-01046-y"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ambrosio, L.F., Insfran, C., Volpini, X., Acosta Rodriguez, E., Serra, H.M., Quintana, F.J., Cervi, L., and Motr\u00e1n, C.C. (2019). Role of Aryl Hydrocarbon Receptor (AhR) in the Regulation of Immunity and Immunopathology During Trypanosoma cruzi Infection. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00631"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"M\u00fcnck, N.A., Roth, J., Sunderk\u00f6tter, C., and Ehrchen, J. (2019). Aryl Hydrocarbon Receptor-Signaling Regulates Early Leishmania major-Induced Cytokine Expression. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02442"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1093\/bioinformatics\/btu781","article-title":"QuasR: Quantification and annotation of short reads in R","volume":"31","author":"Gaidatzis","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e585","DOI":"10.1002\/cpz1.585","article-title":"Exploring Epigenomic Datasets by ChIPseeker","volume":"2","author":"Wang","year":"2022","journal-title":"Curr. Protoc."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","article-title":"Minfi: A flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays","volume":"30","author":"Aryee","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Pidsley, R., Wong, C.C.Y., Volta, M., Lunnon, K., Mill, J., and Schalkwyk, L.C. (2013). A data-driven approach to preprocessing Illumina 450K methylation array data. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-293"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1093\/bioinformatics\/bty778","article-title":"Differential methylation values in differential methylation analysis","volume":"35","author":"Xie","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: A flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1093\/ije\/dyr238","article-title":"Bump hunting to identify differentially methylated regions in epigenetic epidemiology studies","volume":"41","author":"Jaffe","year":"2012","journal-title":"Int. J. Epidemiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41596-019-0128-8","article-title":"Protocol Update for large-scale genome and gene function analysis with the PANTHER classification system (v.14.0)","volume":"14","author":"Mi","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_88","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_89","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"D39","DOI":"10.1093\/nar\/gkac907","article-title":"AnimalTFDB 4.0: A comprehensive animal transcription factor database updated with variation and expression annotations","volume":"51","author":"Shen","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nbt.1630","article-title":"GREAT improves functional interpretation of cis-regulatory regions","volume":"28","author":"McLean","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/bib\/bbs038","article-title":"The UCSC genome browser and associated tools","volume":"14","author":"Kuhn","year":"2013","journal-title":"Brief. Bioinform."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/89\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:00:17Z","timestamp":1760115617000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/89"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,26]]},"references-count":92,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26010089"],"URL":"https:\/\/doi.org\/10.3390\/ijms26010089","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,26]]}}}