Other
24 Authors
- Tang F,
- Coppieters K,
- Dongre A,
- Li F,
- Jiang M,
- Xiao J,
- Smith H,
- Li X,
- Wang C,
- Chen X,
- Leonard WJ,
- McKarns SC,
- Yamamoto E,
- Martin BN,
- Gu C,
- Sartor RB,
- Xian Y,
- Husni ME,
- Jørgensen TN,
- Wang H,
- Zhang CJ,
- Gao J,
- Shi FD,
- Carman J
| First Author | Zhang CJ | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 2745 |
| PubMed ID | 30013031 | Mgi Jnum | J:266316 |
| Mgi Id | MGI:6209177 | Doi | 10.1038/s41467-018-04974-3 |
| Citation | Zhang CJ, et al. (2018) Act1 is a negative regulator in T and B cells via direct inhibition of STAT3. Nat Commun 9(1):2745 |
| abstractText | Although Act1 (adaptor for IL-17 receptors) is necessary for IL-17-mediated inflammatory responses, Act1- (but not Il17ra-, Il17rc-, or Il17rb-) deficient mice develop spontaneous SLE- and Sjogren's-like diseases. Here, we show that Act1 functions as a negative regulator in T and B cells via direct inhibition of STAT3. Mass spectrometry analysis detected an Act1-STAT3 complex, deficiency of Act1 (but not Il17ra-, Il17rc-, or Il17rb) results in hyper IL-23- and IL-21-induced STAT3 activation in T and B cells, respectively. IL-23R deletion or blockade of IL-21 ameliorates SLE- and Sjogren's-like diseases in Act1(-/-) mice. Act1 deficiency results in hyperactivated follicular Th17 cells with elevated IL-21 expression, which promotes T-B cell interaction for B cell expansion and antibody production. Moreover, anti-IL-21 ameliorates the SLE- and Sjogren's-like diseases in Act1-deficient mice. Thus, IL-21 blocking antibody might be an effective therapy for treating SLE- and Sjogren's-like syndrome in patients containing Act1 mutation. |
