A model of TH17-associated ileal hyperplasia that requires both IL-17A and IFNγ to generate self-tolerance and prevent colitis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-07

AUTHORS

Jonathan C. Jeschke, Christopher G. Mayne, Jennifer Ziegelbauer, Christopher L. DeCiantis, Selina Singh, Suresh N. Kumar, Mariko Suchi, Yoichiro Iwakura, William R. Drobyski, Nita H Salzman, Calvin B. Williams

ABSTRACT

Homeostasis in the ileum, which is commonly disrupted in patients with Crohn's disease, involves ongoing immune responses. To study how homeostatic processes of the ileum impact CD4+T cell responses, we used TCR transgenic tools to breed mice that spontaneously produced CD4+T cells reactive to an antigen expressed in the ileum. At an early age, the ilea of these mice exhibit crypt hyperplasia and accumulate increased numbers of TH17 cells bearing non-transgenic clonotypes. Half of these mice subsequently developed colitis linked to broad mucosal infiltration by TH17 and TH1 cells expressing non-transgenic clonotypes, chronic wasting disease and loss of ileal crypt hyperplasia. By contrast, adult mice with normal growth continued to exhibit TH17-associated ileal crypt hyperplasia and additionally accumulated ileal-reactive Treg cells. Both IL-17A and IFNγ were protective, as their deficiency precluded ileal-reactive Treg accumulation and exacerbated colitic disease. IL-23R blockade prevented progression to colitis, whereas nTreg cell transfers prevented colitic disease, ileal crypt hyperplasia and ileal-reactive Treg accumulation. Thus, our studies identify an IL-17A and IFNγ-dependent homeostatic process that mobilizes ileal-reactive Treg cells and is disrupted by IL-23. More... »

PAGES

1127-1137

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41385-018-0023-6

DOI

http://dx.doi.org/10.1038/s41385-018-0023-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1103754034

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29728642


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RDF/XML is a standard XML format for linked data.

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294 Department of Pediatrics, Section of Rheumatology, Medical College of Wisconsin, 53226, Milwaukee, WI, USA
295 rdf:type schema:Organization
296 https://www.grid.ac/institutes/grid.419082.6 schema:alternateName Japan Science and Technology Agency
297 schema:name Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, 332-0012, Saitama, Japan
298 Research Institute for Biomedical Sciences, Tokyo University of Science, 278-0022, Chiba, Japan
299 rdf:type schema:Organization
 




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