期刊
IMMUNITY
卷 49, 期 1, 页码 66-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2018.05.012
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资金
- National Natural Science Foundation of China [81630058, 81570211, 91542107, 31670904]
- Tsinghua University-Peking University Jointed Center for Life Sciences
Genetic mutations of CARD14 (encoding CARMA2) are observed in psoriasis patients. Here we showed that Card14(E138A/+) and Card14(Delta Q136/+) 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-kappa B 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-kappa B activation in keratinocytes in psoriatic initiation.
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