| First Author | Pisitkun P | Year | 2012 |
| Journal | Immunity | Volume | 37 |
| Issue | 6 | Pages | 1104-15 |
| PubMed ID | 23123062 | Mgi Jnum | J:191090 |
| Mgi Id | MGI:5460940 | Doi | 10.1016/j.immuni.2012.08.014 |
| Citation | Pisitkun P, et al. (2012) Interleukin-17 cytokines are critical in development of fatal lupus glomerulonephritis. Immunity 37(6):1104-15 |
| abstractText | Systemic lupus erythematosus is a potentially fatal autoimmune disease. Although interleukin-17 (IL-17) has been linked to human lupus and mouse models of this disease, it has not been addressed whether this cytokine plays a critical role in fatal lupus pathology. Here we have demonstrated that increased production of IL-17 cytokines and their signaling via the adaptor protein CIKS (a.k.a. Traf3ip2, Act1) critically contributed to lethal pathology in an FcgammaR2b-deficient mouse model of lupus. Mice lacking IL-17 and especially those lacking CIKS showed greatly improved survival and were largely protected from development of glomerulonephritis. Importantly in this model, potential effects of IL-17 cytokines on antibody production could be distinguished from critical local contributions in kidneys, including recruitment of neutrophils and monocytes. These findings provide the proof of principle that signaling by IL-17 family cytokines mediated via CIKS presents promising therapeutic targets for the treatment of systemic lupus erythematosus, especially in cases with kidney involvement. |
