First Author | Kashiwagi M | Year | 2017 |
Journal | Nat Immunol | Volume | 18 |
Issue | 3 | Pages | 334-343 |
PubMed ID | 28092372 | Mgi Jnum | J:259948 |
Mgi Id | MGI:6141735 | Doi | 10.1038/ni.3661 |
Citation | Kashiwagi M, et al. (2017) Direct control of regulatory T cells by keratinocytes. Nat Immunol 18(3):334-343 |
abstractText | Environmental challenges to epithelial cells trigger gene expression changes that elicit context-appropriate immune responses. We found that the chromatin remodeler Mi-2beta controls epidermal homeostasis by regulating the genes involved in keratinocyte and immune-cell activation to maintain an inactive state. Mi-2beta depletion resulted in rapid deployment of both a pro-inflammatory and an immunosuppressive response in the skin. A key target of Mi-2beta in keratinocytes is the pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP). Loss of TSLP receptor (TSLPR) signaling specifically in regulatory T (Treg) cells prevented their activation and permitted rapid progression from a skin pro-inflammatory response to a lethal systemic condition. Thus, in addition to their well-characterized role in pro-inflammatory responses, keratinocytes also directly support immune-suppressive responses that are critical for re-establishing organismal homeostasis. |