| First Author | Kumar B | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 2786 |
| PubMed ID | 35589717 | Mgi Jnum | J:338964 |
| Mgi Id | MGI:7283348 | Doi | 10.1038/s41467-022-30437-x |
| Citation | Kumar B, et al. (2022) The ubiquitin ligase Cul5 regulates CD4(+) T cell fate choice and allergic inflammation. Nat Commun 13(1):2786 |
| abstractText | Antigen encounter directs CD4(+) T cells to differentiate into T helper or regulatory cells. This process focuses the immune response on the invading pathogen and limits tissue damage. Mechanisms that govern T helper cell versus T regulatory cell fate remain poorly understood. Here, we show that the E3 ubiquitin ligase Cul5 determines fate selection in CD4(+) T cells by regulating IL-4 receptor signaling. Mice lacking Cul5 in T cells develop Th2 and Th9 inflammation and show pathophysiological features of atopic asthma. Following T cell activation, Cul5 forms a complex with CIS and pJak1. Cul5 deletion reduces ubiquitination and subsequent degradation of pJak1, leading to an increase in pJak1 and pSTAT6 levels and reducing the threshold of IL-4 receptor signaling. As a consequence, Cul5 deficient CD4(+) T cells deviate from Treg to Th9 differentiation in low IL-4 conditions. These data support the notion that Cul5 promotes a tolerogenic T cell fate choice and reduces susceptibility to allergic asthma. |
