{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T07:36:13Z","timestamp":1769585773134,"version":"3.49.0"},"reference-count":26,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T00:00:00Z","timestamp":1749254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"USDA-ARS bovine project","award":["8042-32000-105-00-D"],"award-info":[{"award-number":["8042-32000-105-00-D"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Mouse models serve as a means of examining immune changes when genes of interest are knocked out (KO). One group of immune gene-producing cells that have been identified is type 2 innate lymphoid cells (Ilc2). These cells are involved in the production of Th2 equivalent immune responses and signal cytokine production during the resolution of Nippostrongylus brasiliensis parasite infection in mice lungs. However, many questions about Ilc2 activity in the gut remain. To study this, retinoic acid receptor (RAR)-related orphan receptor alpha (ROR\u03b1)-deficient mice were infected with adult N. brasiliensis and arranged into four treatment groups. Ten days post-infection (dpi), mouse ileum tissue was extracted for RNA-Seq. The ROR\u03b1-deficient mice showed little change in gene expression at 10 dpi (N = 51) when compared to the WT mice at 10 dpi (N = 915), displaying dysregulation within the mouse gut. Based on the results, the gene expression in the gut of Ilc2-deficient mice denoted that the inability to craft Ilc2 cells left the mice unable to mount classical helminth immune responses involving humoral, mast cell, and antibody Th2-driven reactions. Overall, the results showed the importance of Ilc2 in the gut during N. brasiliensis infections and the effect that the lack of these cells had on immunity.<\/jats:p>","DOI":"10.3390\/pathogens14060571","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T06:46:01Z","timestamp":1749451561000},"page":"571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Type 2 Innate Lymphoid Cell (Ilc2)-Deficient Mice Are Transcriptionally Constrained During Nippostrongylus brasiliensis Infection"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8377-0032","authenticated-orcid":false,"given":"Damarius S.","family":"Fleming","sequence":"first","affiliation":[{"name":"USDA-ARS, Beltsville Agricultural Research Center, Animal Parasitic Diseases Laboratory, Beltsville, MD 20705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Public Health, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Joseph F.","family":"Urban","sequence":"additional","affiliation":[{"name":"USDA-ARS, Beltsville Agricultural Research Center, Animal Parasitic Diseases Laboratory, Beltsville, MD 20705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9220-7049","authenticated-orcid":false,"given":"Robert W.","family":"Li","sequence":"additional","affiliation":[{"name":"USDA-ARS, Beltsville Agricultural Research Center, Animal Parasitic Diseases Laboratory, Beltsville, MD 20705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fricke, W.F., Song, Y., Wang, A.J., Smith, A., Grinchuk, V., Mongodin, E., Pei, C., Ma, B., Lu, N., and Urban, J.F. (2015). Type 2 immunity-dependent reduction of segmented filamentous bacteria in mice infected with the helminthic parasite Nippostrongylus brasiliensis. Microbiome, 3, Erratum in Microbiome 2015, 3, 77. https:\/\/doi.org\/10.1186\/s40168-015-0142-1.","DOI":"10.1186\/s40168-015-0142-1"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e12429","DOI":"10.1111\/pim.12429","article-title":"The role of ILC2 in hookworm infection","volume":"40","author":"Filbey","year":"2018","journal-title":"Parasite Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1126\/science.aaf1648","article-title":"Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut","volume":"351","author":"Howitt","year":"2016","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.immuni.2015.06.009","article-title":"Retinoic Acid Differentially Regulates the Migration of Innate Lymphoid Cell Subsets to the Gut","volume":"43","author":"Kim","year":"2015","journal-title":"Immunity"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1093\/embo-reports\/kve007","article-title":"The orphan nuclear receptor ROR alpha is a negative regulator of the inflammatory response","volume":"2","author":"Delerive","year":"2001","journal-title":"EMBO Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Haim-Vilmovsky, L., Henriksson, J., Walker, J.A., Miao, Z., Natan, E., Kar, G., Clare, S., Barlow, J.L., Charidemou, E., and Mamanova, L. (2021). Mapping Rora expression in resting and activated CD4+ T cells. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251233"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1038\/ni.3244","article-title":"Innate immunological function of TH2 cells in vivo","volume":"16","author":"Guo","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1126\/science.1247606","article-title":"Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity","volume":"343","author":"Spencer","year":"2014","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1093\/bioinformatics\/btq281","article-title":"Manipulation of FASTQ data with Galaxy","volume":"26","author":"Blankenberg","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"D988","DOI":"10.1093\/nar\/gkab1049","article-title":"Ensembl 2022","volume":"50","author":"Cunningham","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D52","DOI":"10.1093\/nar\/gkq1237","article-title":"Entrez Gene: Gene-centered information at NCBI","volume":"39","author":"Maglott","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"D523","DOI":"10.1093\/nar\/gkac1052","article-title":"UniProt: The Universal Protein Knowledgebase in 2023","volume":"51","author":"UniProt","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Samuelson, E.M., Laird, R.M., Papillion, A.M., Tatum, A.H., Princiotta, M.F., and Hayes, S.M. (2014). Reduced B lymphoid kinase (Blk) expression enhances proinflammatory cytokine production and induces nephrosis in C57BL\/6-lpr\/lpr mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092054"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Haydar, D., Gonzalez, R., Garvy, B.A., Garneau-Tsodikova, S., Thamban Chandrika, N., Bocklage, T.J., and Feola, D.J. (2021). Myeloid arginase-1 controls excessive inflammation and modulates T cell responses in Pseudomonas aeruginosa pneumonia. Immunobiology, 226.","DOI":"10.1016\/j.imbio.2020.152034"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sutherland, T.E., R\u00fcckerl, D., Logan, N., Duncan, S., Wynn, T.A., and Allen, J.E. (2018). Ym1 induces RELM\u03b1 and rescues IL-4R\u03b1 deficiency in lung repair during nematode infection. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007423"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1681\/ASN.2015040422","article-title":"MicroRNA-196a\/b Mitigate Renal Fibrosis by Targeting TGF-beta Receptor 2","volume":"27","author":"Meng","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jdermsci.2020.08.010","article-title":"Acute skin barrier disruption alters the secretion of lamellar bodies via the multilayered expression of ABCA12","volume":"100","author":"Teramura","year":"2020","journal-title":"J. Dermatol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1093\/infdis\/jiy151","article-title":"NKG2D Regulation of Lung Pathology and Dendritic Cell Function Following Respiratory Syncytial Virus Infection","volume":"218","author":"Liu","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"761","DOI":"10.4049\/jimmunol.1601416","article-title":"TLR9 Regulates the NF-\u03baB-NLRP3-IL-1\u03b2 Pathway Negatively in Salmonella-Induced NKG2D-Mediated Intestinal Inflammation","volume":"199","author":"Li","year":"2017","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/intimm\/dxab012","article-title":"Alleviation of colonic inflammation by Lypd8 in a mouse model of inflammatory bowel disease","volume":"33","author":"Hsu","year":"2021","journal-title":"Int. Immunol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/6\/571\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:48:09Z","timestamp":1760032089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/6\/571"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,7]]},"references-count":26,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["pathogens14060571"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14060571","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,7]]}}}