McNamee, Eóin N., Masterson, Joanne C., Veny, Marisol, Collins, Colm B., Jedlicka, Paul, Byrne, Fergus R., Ng, Gordon Y. and Rivera-Nieves, Jesus (2015) Chemokine receptor CCR7 regulates the intestinal TH1/TH17/Treg balance during Crohn’s-like murine ileitis. Journal Of Leukocyte Biology, 97 (6). pp. 1011-1022. ISSN 1938-3673
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Abstract
The regulation of T cell and DC retention and lymphatic egress within and from the intestine is critical for intestinal immunosurveillance; however, the cellular processes that orchestrate this balance during IBD remain poorly defined. With the use of a mouse model of TNF-driven Crohn's-like ileitis (TNF(Δ) (ARE)), we examined the role of CCR7 in the control of intestinal T cell and DC retention/egress during experimental CD. We observed that the frequency of CCR7-expressing TH1/TH17 effector lymphocytes increased during active disease in TNF(Δ) (ARE) mice and that ΔARE/CCR7(-/-) mice developed exacerbated ileitis and multiorgan inflammation, with a marked polarization and ileal retention of TH1 effector CD4(+) T cells. Furthermore, adoptive transfer of ΔARE/CCR7(-/-) effector CD4(+) into lymphopenic hosts resulted in ileo-colitis, whereas those transferred with ΔARE/CCR7(+/+) CD4(+) T cells developed ileitis. ΔARE/CCR7(-/-) mice had an acellular draining MLN, decreased CD103(+) DC, and decreased expression of RALDH enzymes and of CD4(+)CD25(+)FoxP3(+) Tregs. Lastly, a mAb against CCR7 exacerbated ileitis in TNF(Δ) (ARE) mice, phenocopying the effects of congenital CCR7 deficiency. Our data underscore a critical role for the lymphoid chemokine receptor CCR7 in orchestrating immune cell traffic and TH1 versus TH17 bias during chronic murine ileitis.
Item Type: | Article |
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Keywords: | Chemokine; receptor; CCR7; regulates; intestinal; TH1/TH17/Treg; balance; Crohn’s-like murine ileitis; Crohns; |
Academic Unit: | Faculty of Science and Engineering > Biology |
Item ID: | 12479 |
Identification Number: | 10.1189/jlb.3HI0614-303R |
Depositing User: | Joanne Masterson |
Date Deposited: | 26 Feb 2020 16:06 |
Journal or Publication Title: | Journal Of Leukocyte Biology |
Publisher: | Wiley Online Library |
Refereed: | Yes |
Related URLs: | |
URI: | https://mural.maynoothuniversity.ie/id/eprint/12479 |
Use Licence: | This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here |
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