GSDME deficiency leads to the aggravation of UVB-induced skin inflammation through enhancing recruitment and activation of neutrophils

被引：30

作者：

Chen, Yujie ^{[1
]}

Lian, Ni ^{[1
]}

Chen, Sihan ^{[1
]}

Xiao, Ta ^{[1
]}

Ke, Yangying ^{[1
]}

Zhang, Yiqun ^{[1
]}

Song, Changjun ^{[1
]}

Yang, Yong ^{[1
]}

Xu, Song ^{[1
]}

Gu, Heng ^{[1
]}

Chen, Xu ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Dermatol, Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing 210042, Peoples R China

[2] Chinese Acad Med Sci, Key Lab Basic & Translat Res Immune Mediated Skin, Nanjing, Peoples R China

来源：

CELL DEATH & DISEASE | 2022年 / 13卷 / 10期

基金：

中国国家自然科学基金;

关键词：

CELL-DEATH; PYROPTOSIS; IMMUNITY; CLEAVAGE;

D O I：

10.1038/s41419-022-05276-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-alpha 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.

引用

页数：14

共 37 条

[21] Lipocalin-2: A Master Mediator of Intestinal and Metabolic Inflammation [J].