| First Author | Zhou V | Year | 2016 |
| Journal | J Clin Invest | Volume | 126 |
| Issue | 9 | Pages | 3541-55 |
| PubMed ID | 27500496 | Mgi Jnum | J:237249 |
| Mgi Id | MGI:5811739 | Doi | 10.1172/JCI80874 |
| Citation | Zhou V, et al. (2016) A colitogenic memory CD4+ T cell population mediates gastrointestinal graft-versus-host disease. J Clin Invest 126(9):3541-55 |
| abstractText | Damage to the gastrointestinal tract is a major cause of morbidity and mortality in graft-versus-host disease (GVHD) and is attributable to T cell-mediated inflammation. In this work, we identified a unique CD4+ T cell population that constitutively expresses the beta2 integrin CD11c and displays a biased central memory phenotype and memory T cell transcriptional profile, innate-like properties, and increased expression of the gut-homing molecules alpha4beta7 and CCR9. Using several complementary murine GVHD models, we determined that adoptive transfer and early accumulation of beta2 integrin-expressing CD4+ T cells in the gastrointestinal tract initiated Th1-mediated proinflammatory cytokine production, augmented pathological damage in the colon, and increased mortality. The pathogenic effect of this CD4+ T cell population critically depended on coexpression of the IL-23 receptor, which was required for maximal inflammatory effects. Non-Foxp3-expressing CD4+ T cells produced IL-10, which regulated colonic inflammation and attenuated lethality in the absence of functional CD4+Foxp3+ T cells. Thus, the coordinate expression of CD11c and the IL-23 receptor defines an IL-10-regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers. |
