{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T23:40:25Z","timestamp":1773099625577,"version":"3.50.1"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Th17 cells play a role as an inflammation mediator in a variety of autoimmune disorders, including inflammatory bowel disease, and thus are widely considered to be pathogenic. However, Th17 cells are present in the normal intestine and show a homeostatic phenotype; that is, they participate in the maintenance of intestinal homeostasis rather than inducing inflammation. We observed an enlarged Th17 population in the small intestine of C57BL\/6.IgA\u2212\/\u2212 mice compared with wild-type mice, which was further amplified with cholera toxin (CT) immunization without causing intestinal inflammation. The increased Th17 induction and the correspondingly 10-fold higher CT B subunit\u2013specific serum IgG response in IgA\u2212\/\u2212 mice after CT immunization was microbiota dependent and was associated with increased segmented filamentous bacteria in the small intestine of IgA\u2212\/\u2212 mice. Oral administration of vancomycin greatly dampened both CT immunogenicity and adjuvanticity, and the differential CT responses in IgA\u2212\/\u2212 and wild-type mice disappeared after intestinal microbiota equalization. Using gnotobiotic mouse models, we found that CT induction of homeostatic intestinal Th17 responses was supported not only by segmented filamentous bacteria, but also by other commensal bacteria. Furthermore, transcriptome analysis using IL-17AhCD2 reporter mice revealed a similar gene expression profile in CT-induced intestinal Th17 cells and endogenous intestinal Th17 cells at homeostasis, with upregulated expression of a panel of immune-regulatory genes, which was distinctly different from the gene expression profile of pathogenic Th17 cells. Taken together, we identified a nonpathogenic signature of intestinal homeostatic Th17 cells, which are actively regulated by the commensal microbiota and can be selectively stimulated by CT.<\/jats:p>","DOI":"10.4049\/jimmunol.1700171","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T00:40:23Z","timestamp":1495672823000},"page":"312-322","source":"Crossref","is-referenced-by-count":21,"title":["Selective Induction of Homeostatic Th17 Cells in the Murine Intestine by Cholera Toxin Interacting with the Microbiota"],"prefix":"10.1093","volume":"199","author":[{"given":"Qing","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacey N","family":"Harbour","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raivo","family":"Kolde","sequence":"additional","affiliation":[{"name":"Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0638-1783","authenticated-orcid":false,"given":"Isabel J","family":"Latorre","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard , Cambridge, MA 02142"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7597-5062","authenticated-orcid":false,"given":"Hein M","family":"Tun","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Manitoba , Winnipeg, Manitoba R3T 2N2,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trenton R","family":"Schoeb","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrietta","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8246-931X","authenticated-orcid":false,"given":"James J","family":"Moon","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehsan","family":"Khafipour","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Manitoba , Winnipeg, Manitoba R3T 2N2,","place":["Canada"]},{"name":"Department of Medical Microbiology, University of Manitoba , Winnipeg, Manitoba R3T 2N2,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramnik J","family":"Xavier","sequence":"additional","affiliation":[{"name":"Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"},{"name":"Broad Institute of MIT and Harvard , Cambridge, MA 02142"},{"name":"Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casey T","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL 35294"},{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8873-1534","authenticated-orcid":false,"given":"Charles O","family":"Elson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL 35294"},{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,7,1]]},"reference":[{"key":"2025030612102147700_r1","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1126\/science.1124234","article-title":"Metagenomic analysis of the human distal gut microbiome","volume":"312","author":"Gill","year":"2006","journal-title":"Science"},{"key":"2025030612102147700_r2","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature11551","article-title":"Reciprocal interactions of the intestinal microbiota and immune 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