Keratinocyte transglutaminase 2 promotes CCR6+ γδT-cell recruitment by upregulating CCL20 in psoriatic inflammation
| Autor: | In Gyu Kim, Jin Haeng Lee, Eui Man Jeong, Seok Jin Lee, Mee ae Kwon, Hyo Jun Kim, Ki Baek Lee, Jinha Hwang, Ji Woong Shin, Jin Ho Chung, Soojin Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Leukocyte migration Chemokine biology Chemistry lcsh:Cytology Immunology Inflammation Cell Biology medicine.disease CCL20 Cellular and Molecular Neuroscience medicine.anatomical_structure Immune system Downregulation and upregulation Psoriasis medicine Cancer research biology.protein medicine.symptom lcsh:QH573-671 Keratinocyte |
| Zdroj: | Cell Death and Disease, Vol 11, Iss 4, Pp 1-14 (2020) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-020-2495-z |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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