| First Author | Havenar-Daughton C | Year | 2012 |
| Journal | Blood | Volume | 119 |
| Issue | 15 | Pages | 3486-94 |
| PubMed ID | 22371886 | Mgi Jnum | J:183768 |
| Mgi Id | MGI:5319248 | Doi | 10.1182/blood-2012-01-401604 |
| Citation | Havenar-Daughton C, et al. (2012) Development and function of murine RORgammat(+) iNKT cells are under TGF-beta signaling control. Blood 119(15):3486-94 |
| abstractText | Invariant natural killer T (iNKT) cells have the ability to rapidly secret cytokines in response to diverse stimuli, and therefore influence numerous immune reactions. Although IFN-gamma and IL-4 are thought to dominate iNKT cytokine production, a distinct subset of iNKT cells, expressing RORgammat and producing IL-17, has now been identified in both mice and humans. Although a role in pathogen and allergic responses has been assigned to the RORgammat(+) iNKT subset, factors controlling their development and function remain illusive. Here, we demonstrate that RORgammat(+) iNKT-cell differentiation obeys transforming growth factor-beta (TGF-beta) signaling control, different from that described for conventional iNKT cells. We reveal that TGF-beta signaling, and particularly its SMAD4-dependent pathway, is required for both the survival of RORgammat(+) iNKT cells during their development and IL-17 production at the periphery. Moreover, constitutive TGF-beta signaling in RORgammat(+) iNKT cells drives higher peripheral numbers and increased tissue distribution. Finally, we found that SMAD4-dependent TGF-beta signaling is mandatory for the peripheral expansion of the RORgammat(+) iNKT cells responding to inflammatory signals. Thus, this work demonstrates that both the development and responsiveness of the newly described IL-17-producing iNKT cell subset is under the control of a dedicated TGF-beta signaling pathway. |
