| First Author | Wang M | Year | 2018 |
| Journal | Immunity | Volume | 49 |
| Issue | 1 | Pages | 66-79.e5 |
| PubMed ID | 29980436 | Mgi Jnum | J:289239 |
| Mgi Id | MGI:6434705 | Doi | 10.1016/j.immuni.2018.05.012 |
| Citation | Wang M, et al. (2018) Gain-of-Function Mutation of Card14 Leads to Spontaneous Psoriasis-like Skin Inflammation through Enhanced Keratinocyte Response to IL-17A. Immunity 49(1):66-79.e5 |
| abstractText | Genetic mutations of CARD14 (encoding CARMA2) are observed in psoriasis patients. Here we showed that Card14(E138A/+) and Card14(DeltaQ136/+) mice developed spontaneous psoriasis-like skin inflammation, which resulted from constitutively activated CARMA2 via self-aggregation leading to the enhanced activation of the IL-23-IL-17A cytokine axis. Card14(-/-) mice displayed attenuated skin inflammation in the imiquimod-induced psoriasis model due to impaired IL-17A signaling in keratinocytes. CARMA2, mainly expressed in keratinocytes, associates with the ACT1-TRAF6 signaling complex and mediates IL-17A-induced NF-kappaB and MAPK signaling pathway activation, which leads to expression of pro-inflammatory factors. Thus, CARMA2 serves as a key mediator of IL-17A signaling and its constitutive activation in keratinocytes leads to the onset of psoriasis, which indicates an important role of NF-kappaB activation in keratinocytes in psoriatic initiation. |
