| First Author | Ma J | Year | 2019 |
| Journal | Sci Signal | Volume | 12 |
| Issue | 602 | PubMed ID | 31594855 |
| Mgi Jnum | J:284324 | Mgi Id | MGI:6380834 |
| Doi | 10.1126/scisignal.aao3829 | Citation | Ma J, et al. (2019) CARD9 mediates dendritic cell-induced development of Lyn deficiency-associated autoimmune and inflammatory diseases. Sci Signal 12(602) |
| abstractText | CARD9 is an immune adaptor protein in myeloid cells that is involved in C-type lectin signaling and antifungal immunity. CARD9 is implicated in autoimmune and inflammatory-related diseases, such as rheumatoid arthritis, IgA nephropathy, ankylosing spondylitis, and inflammatory bowel disease (IBD). Given that Lyn-deficient (Lyn(-/-)) mice are susceptible to both autoimmunity and IBD, we investigated the immunological role of CARD9 in the development of these diseases using the Lyn(-/-) mouse model. We found that genetic deletion of CARD9 was sufficient to reduce the development of both spontaneous autoimmune disease as well as DSS- or IL-10 deficiency-associated colitis in Lyn(-/-) mice. Mechanistically, CARD9 was a vital component of the Lyn-mediated regulation of Toll-like receptor (TLR2 and TLR4) signaling in dendritic cells, but not in macrophages. In the absence of Lyn, signaling through a CD11b-Syk-PKCdelta-CARD9 pathway was amplified, leading to increased TLR-induced production of inflammatory cytokines. Dendritic cell-specific deletion of CARD9 reversed the development of autoimmune and experimental colitis observed in dendritic cell-specific, Lyn-deficient mice. These findings suggest that targeting CARD9 may suppress the development of colitis and autoimmunity by reducing dendritic cell-driven inflammation. |
