| First Author | Singh AK | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 4603 | PubMed ID | 25091235 |
| Mgi Jnum | J:225210 | Mgi Id | MGI:5691861 |
| Doi | 10.1038/ncomms5603 | Citation | Singh AK, et al. (2014) DOCK8 regulates protective immunity by controlling the function and survival of RORgammat+ ILCs. Nat Commun 5:4603 |
| abstractText | Retinoic acid receptor-related orphan receptor-gammat-positive (RORgammat(+)) innate lymphoid cells (ILCs) produce interleukin (IL)-22 and IL-17, which are critical for protective immunity against enteric pathogens. The molecular mechanism underlying the development and survival of RORgammat(+) ILCs is not thoroughly understood. Here, we show that Dedicator of cytokinesis 8 (DOCK8), a scaffolding protein involved in cytoskeletal rearrangement and cell migration, is essential for the protective immunity against Citrobacter rodentium. A comparative RNA sequencing-based analysis reveals an impaired induction of antimicrobial peptides in the colon of DOCK8-deficient mice, which correlates with high susceptibility to infection and a very low number of IL-22-producing RORgammat(+) ILCs in their GI tract. Furthermore, DOCK8-deficient RORgammat(+) ILCs are less responsive to IL-7 mediated signalling, more prone to apoptosis and produce less IL-22 due to a defect in IL-23-mediated STAT3 phosphorylation. Our studies reveal an unsuspected role of DOCK8 for the function, generation and survival of RORgammat(+) ILCs. |
