onr:"swepub:oai:gup.ub.gu.se/299729"
Search: onr:"swepub:oai:gup.ub.gu.se/299729" > PTPN2 links colonic...
- 1 of 1
- Previous record
- Next record
- To hitlist
PTPN2 links colonic and joint inflammation in experimental autoimmune arthritis
- Hsieh, W. C. (author)
-
- Svensson, Mattias, 1982 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
- Zoccheddu, M. (author)
- show more...
- Tremblay, M. L. (author)
- Sakaguchi, S. (author)
- Stanford, S. M. (author)
- Bottini, N. (author)
- show less...
- (creator_code:org_t)
- 2020-10-15
- 2020
- English.
- In: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 5:20
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Loss-of-function variants of protein tyrosine phosphatase non-receptor type 2 (PTPN2) enhance risk of inflammatory bowel disease and rheumatoid arthritis; however, whether the association between PTPN2 and autoimmune arthritis depends on gut inflammation is unknown. Here we demonstrate that induction of subclinical intestinal inflammation exacerbates development of autoimmune arthritis in SKG mice. Ptpn2-haploinsufficient SKG mice - modeling human carriers of disease-associated variants of PTPN2 - displayed enhanced colitis-induced arthritis and joint accumulation of Tregs expressing RAR-related orphan receptor gamma T (ROR-gamma t) - a gut-enriched Treg subset that can undergo conversion into FoxP3 IL-17(+) arthritogenic exTregs. SKG colonic Tregs underwent higher conversion into arthritogenic exTregs when compared with peripheral Tregs, which was exacerbated by haploinsufficiency of Ptpn2. Ptpn2 haploinsufficiency led to selective joint accumulation of ROR gamma t-expressing Tregs expressing the colonic marker G protein-coupled receptor 15 (GPR15) in arthritic mice and selectively enhanced conversion of GPR15(+). Tregs into exTregs in vitro and in vivo. Inducible Treg-specific haploinsufficiency of Ptpn2 enhanced colitis-induced SKG arthritis and led to specific joint accumulation of GPR15(+). exTregs. Our data validate the SKG model for studies at the interface between intestinal and joint inflammation and suggest that arthritogenic variants of PTPN2 amplify the link between gut inflammation and arthritis through conversion of colonic Tregs into exTregs.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Hsieh, W. C.
- Svensson, Mattia ...
- Zoccheddu, M.
- Tremblay, M. L.
- Sakaguchi, S.
- Stanford, S. M.
- show more...
- Bottini, N.
- show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Clinical Medicin ...
- Articles in the publication
- Jci Insight
- By the university
- University of Gothenburg
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
