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- Title
Keratinocyte transglutaminase 2 promotes CCR6+ γδT-cell recruitment by upregulating CCL20 in psoriatic inflammation.
- Authors
Shin, Ji-Woong; Kwon, Mee-ae; Hwang, Jinha; Lee, Seok-Jin; Lee, Jin-Haeng; Kim, Hyo-Jun; Lee, Ki Baek; Lee, Soo-Jin; Jeong, Eui Man; Chung, Jin Ho; Kim, In-Gyu
- Abstract
Keratinocyte-derived cytokines and chemokines amplify psoriatic inflammation by recruiting IL-17-producing CCR6+ γδT-cells and neutrophils. The expression of these cytokines and chemokines mainly depends on NF-κB activity; however, the pathway that activates NF-κB in response to triggering factors is poorly defined. Here, we show that transglutaminase 2 (TG2), previously reported to elicit a TH17 response by increasing IL-6 expression in a mouse model of lung fibrosis, mediates the upregulation of cytokines and chemokines by activating NF-κB in imiquimod (IMQ)-treated keratinocytes. TG2-deficient mice exhibited reduced psoriatic inflammation in skin treated with IMQ but showed systemic immune responses similar to wild-type mice. Experiments in bone marrow (BM) chimeric mice revealed that TG2 is responsible for promoting psoriatic inflammation in non-BM-derived cells. In keratinocytes, IMQ treatment activated TG2, which in turn activated NF-κB signaling, leading to the upregulation of IL-6, CCL20, and CXCL8 and increased leukocyte migration, in vitro. Consequently, TG2-deficient mice showed markedly decreased CCR6+ γδT-cell and neutrophil infiltration in IMQ-treated skin. Moreover, TG2 levels were higher in psoriatic skin than in normal skin and correlated with IL-6, CXCL8, and CCL20 levels. Therefore, these results indicate that keratinocyte TG2 acts as a critical mediator in the amplification of psoriatic inflammation.
- Publication
Cell Death & Disease, 2020, Vol 11, Issue 4, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-020-2495-z