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    Chemokine receptor CCR7 regulates the intestinal TH1/TH17/Treg balance during Crohn’s-like murine ileitis


    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:

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