| First Author | McNamee EN | Year | 2015 |
| Journal | J Leukoc Biol | Volume | 97 |
| Issue | 6 | Pages | 1011-22 |
| PubMed ID | 25637591 | Mgi Jnum | J:317953 |
| Mgi Id | MGI:6837545 | Doi | 10.1189/jlb.3HI0614-303R |
| Citation | McNamee EN, et al. (2015) Chemokine receptor CCR7 regulates the intestinal TH1/TH17/Treg balance during Crohn's-like murine ileitis. J Leukoc Biol 97(6):1011-22 |
| abstractText | 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(Delta) (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(Delta) (ARE) mice and that DeltaARE/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 DeltaARE/CCR7(-/-) effector CD4(+) into lymphopenic hosts resulted in ileo-colitis, whereas those transferred with DeltaARE/CCR7(+/+) CD4(+) T cells developed ileitis. DeltaARE/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(Delta) (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. |
