Keratinocyte transglutaminase 2 promotes CCR6⁺ γδT-cell recruitment by upregulating CCL20 in psoriatic inflammation.

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 T_H17 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) chimeri

SUBMITTER: Shin JW 

PROVIDER: S-EPMC7193648 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature