GPR97 depletion aggravates imiquimod-induced psoriasis pathogenesis via amplifying IL-23/IL-17 axis signal pathway

被引：1

作者：

Gao, Yaoxin ^{[1
,2
]}

Zhan, Weirong ^{[1
]}

Guo, Dandan ^{[1
]}

Lin, Haizhen ^{[1
]}

Farooq, Muhammad Asad ^{[1
]}

Jin, Chenxu ^{[1
]}

Zhang, Li ^{[1
]}

Zhou, Ying ^{[1
]}

Yao, Jie ^{[1
]}

Duan, Yixin ^{[1
]}

He, Cong ^{[3
,4
]}

Jiang, Shuai ^{[5
,6
]}

Jiang, Wenzheng ^{[1
]}

机构：

[1] East China Normal Univ, Sch Life Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China

[2] Zhengzhou Univ, Affiliated Hosp 1, Biotherapy Ctr, Zhengzhou 450052, Henan, Peoples R China

[3] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Urol,Lab Canc Genom & Biol, Shanghai 200080, Peoples R China

[4] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Inst Translat Med, Sch Med, Shanghai 200080, Peoples R China

[5] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200438, Peoples R China

[6] Fudan Univ, Human Phenome Inst, Shanghai 200438, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2024年 / 179卷

基金：

中国国家自然科学基金;

关键词：

Psoriasis; GPR97; DCs; Th17; cells; Keratinocytes; HELPER TYPE 17; NF-KAPPA-B; DENDRITIC CELLS; MOUSE MODEL; AMELIORATES IMIQUIMOD; SKIN INFLAMMATION; PLAQUE-FORMATION; DIFFERENTIATION; DISEASE; MICE;

D O I：

10.1016/j.biopha.2024.117431

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Skin psoriasis is defined as receiving external stimulation to activate skin dendritic cells (DCs) which can release interleukin 23 (IL-23) to interlink the innate and adaptive immunity as well as induce T helper 17 (Th17) cell differentiation leading to elevated production of interleukin 17 (IL-17) for keratinocytes over production. This autoimmune loop in psoriasis pathogenesis is influenced by G protein-coupled receptor (GPCR) signalling transduction, and in particular, function of adhesion molecule GPR97 in psoriasis endures to be utterly addressed. In this research, our team allocated GPR97 depletion (GPR97(-/-)), GPR97 conditional depletion on dendritic cell (DC-cKO), and keratin 14-conditional knockout (K14-cKO) mice models to explore the function of GPR97 which influences keratinocytes and skin immunity. It was found that significantly aggravated psoriasis-like lesion in GPR97(-/-) mice. In addition, hyperproliferative keratinocytes as well as accumulation of DCs and Th17 cells were detected in imiquimod (IMQ)-induced GPR97(-/-) mice, which was consistent with the results in DC-cKO and K14-cKO psoriasis model. Additional investigations indicated that beclomethasone dipropionate (BDP), an agonist of GPR97, attenuated the psoriasis-like skin disease and restricted HaCaT cells abnormal proliferation as well as Th17 cells differentiation. Particularly, we found that level of NF-kappa B p65 was increased in GPR97(-/-) DCs and BDP could inhibit p65 activation in DCs. Role of GPR97 is indispensable and this adhesion receptor may affect immune cell enrichment and function in skin and alter keratinocytes proliferation as well as differentiation in psoriasis.

引用

页数：15

共 67 条

[1] Inhibition of spleen tyrosine kinase attenuates psoriasis-like inflammation in mice through blockade of dendritic cell-Th17 inflammation axis [J].