Bibliographic Details
| Title: |
GSDME deficiency leads to the aggravation of UVB-induced skin inflammation through enhancing recruitment and activation of neutrophils |
| Authors: |
Yujie Chen, Ni Lian, Sihan Chen, Ta Xiao, Yangying Ke, Yiqun Zhang, Changjun Song, Yong Yang, Song Xu, Heng Gu, Xu Chen |
| Source: |
Cell Death and Disease, Vol 13, Iss 10, Pp 1-14 (2022) |
| Publisher Information: |
Nature Publishing Group, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
Cytology, QH573-671 |
| More Details: |
Abstract Gasdermin E (GSDME)-mediated pyroptosis is induced in keratinocytes of UVB-challenged skin. The role of GSDME in UVB-caused skin damage remains unknown. To explore the role of GSDME in UVB-induced skin inflammation. We compared differences in skin appearance, histological features, keratinocyte death modalities, infiltration of immune cells, and levels of some inflammatory cytokines between Gsdme −/− mice and wild type (WT) mice after UVB exposure. We explored whether keratinocytes contribute to GSDME deficiency-caused aggravation of UVB-induced skin inflammation in GSDME knockdown keratinocyte cultured in vitro and keratinocyte-specific Gsdme conditional knockout mice. We used anti-Ly6G antibody to deplete neutrophils and explore their role in UVB-caused skin damage. Skin damage and neutrophils infiltration were aggravated in UVB-challenged Gsdme −/− mice, compared with UVB-challenged WT mice. Apoptosis and necroptosis, which were initiated together with GSDME-mediated pyroptosis in UVB-challenged WT mice, were not enhanced in UVB-challenged Gsdme −/− mice. Neutrophils activation indicators and its recruiting cytokines were increased in skin tissue of UVB-challenged Gsdme −/− mice. However, GSDME knockdown did not lead to the further increase of mRNA and secretion of TNF-α and IL-6 in UVB-challenged keratinocytes. Skin damage was not aggravated in UVB-challenged Gsdme cKO mice. Neutrophils depletion alleviated UVB-caused skin damage in WT mice and Gsdme −/− mice, and eliminated its aggravation in Gsdme −/− mice. This study demonstrates that GSDME plays a restrictive role in UVB-induced skin damage through inhibiting excessive recruitment and activation of neutrophils in the immune microenvironment in UVB-caused skin inflammation. However, keratinocytes might not contribute to this restrictive function. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-4889 |
| Relation: |
https://doaj.org/toc/2041-4889 |
| DOI: |
10.1038/s41419-022-05276-9 |
| Access URL: |
https://doaj.org/article/c71890f249554602bfd22fa05651feae |
| Accession Number: |
edsdoj.71890f249554602bfd22fa05651feae |
| Database: |
Directory of Open Access Journals |
