| First Author | Ban T | Year | 2016 |
| Journal | Immunity | Volume | 45 |
| Issue | 2 | Pages | 319-32 |
| PubMed ID | 27521268 | Mgi Jnum | J:259269 |
| Mgi Id | MGI:6140814 | Doi | 10.1016/j.immuni.2016.07.015 |
| Citation | Ban T, et al. (2016) Lyn Kinase Suppresses the Transcriptional Activity of IRF5 in the TLR-MyD88 Pathway to Restrain the Development of Autoimmunity. Immunity 45(2):319-32 |
| abstractText | Interferon regulatory factor-5 (IRF5), a transcription factor critical for the induction of innate immune responses, contributes to the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) in humans and mice. Lyn, a Src family kinase, is also implicated in human SLE, and Lyn-deficient mice develop an SLE-like disease. Here, we found that Lyn physically interacted with IRF5 to inhibit ubiquitination and phosphorylation of IRF5 in the TLR-MyD88 pathway, thereby suppressing the transcriptional activity of IRF5 in a manner independent of Lyn''s kinase activity. Conversely, Lyn did not inhibit NF-kappaB signaling, another major branch downstream of MyD88. Monoallelic deletion of Irf5 alleviated the hyperproduction of cytokines in TLR-stimulated Lyn(-/-) dendritic cells and the development of SLE-like symptoms in Lyn(-/-) mice. Our results reveal a role for Lyn as a specific suppressor of the TLR-MyD88-IRF5 pathway and illustrate the importance of fine-tuning IRF5 activity for the maintenance of immune homeostasis. |
