McNamee, Eóin N. and Masterson, Joanne C. and Veny, Marisol and Collins, Colm B. and Jedlicka, Paul and Byrne, Fergus R. and 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
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:	https://doi.org/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
URI:	Publisher
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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