| First Author | Fujikado N | Year | 2016 |
| Journal | Immunity | Volume | 45 |
| Issue | 5 | Pages | 999-1012 |
| PubMed ID | 27851927 | Mgi Jnum | J:259743 |
| Mgi Id | MGI:6141599 | Doi | 10.1016/j.immuni.2016.10.023 |
| Citation | Fujikado N, et al. (2016) Aire Inhibits the Generation of a Perinatal Population of Interleukin-17A-Producing gammadelta T Cells to Promote Immunologic Tolerance. Immunity 45(5):999-1012 |
| abstractText | Aire''s primary mechanism of action is to regulate transcription of a battery of genes in medullary thymic epithelial cells (mTECs) and, consequently, negative selection of effector T cells and positive selection of regulatory T cells. We found that Aire-deficient mice had expanded thymic and peripheral populations of perinatally generated IL-17A(+)Vgamma6(+)Vdelta1(+) T cells, considered to be "early responders" to tissue stress and drivers of inflammatory reactions. Aire-dependent control of Il7 expression in mTECs regulated the size of thymic IL-17A(+)Vgamma6(+)Vdelta1(+) compartments. In mice lacking Aire and gammadelta T cells, certain tissues typically targeted in the "Aire-less" disease, notably the retina, were only minimally infiltrated. IL-17A(+)Vgamma6(+)Vdelta1(+) cells were present in the retina of wild-type mice and expanded very early in Aire-deficient mice. A putatively parallel population of IL-17A(+)Vgamma9(+)Vdelta2(+) T cells was increased in humans lacking Aire. Thus, Aire exerts multi-faceted autoimmune control that extends to a population of innate-like T cells. |
