HA/CD44 Regulates the T Helper 1 Cells Differentiation by Activating Annexin A1/Akt/mTOR Signaling to Drive the Pathogenesis of EAP

被引：18

作者：

Chen, Jing ^{[1
,2
,3
]}

Meng, Jialin ^{[1
,2
,3
]}

Li, Xiaoling ^{[1
,2
,3
]}

Li, Xiao ^{[1
,2
,3
]}

Liu, Yi ^{[1
,2
,3
]}

Jin, Chen ^{[1
,2
,3
]}

Zhang, Li ^{[1
,2
,3
]}

Hao, Zongyao ^{[1
,2
,3
]}

Chen, Xianguo ^{[1
,2
,3
]}

Zhang, Meng ^{[1
,2
,3
]}

Liang, Chaozhao ^{[1
,2
,3
]}

机构：

[1] Anhui Med Univ, Dept Urol, Affiliated Hosp 1, Hefei, Peoples R China

[2] Anhui Med Univ, Inst Urol, Hefei, Peoples R China

[3] Anhui Med Univ, Anhui Prov Key Lab Genitourinary Dis, Hefei, Peoples R China

来源：

FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷

基金：

中国国家自然科学基金;

关键词：

chronic prostatitis; chronic pelvic pain syndrome; CD44; hyaluronan; ANX A1; Th1; cells; NONOBESE DIABETIC MICE; AUTOIMMUNE PROSTATITIS; CD44; INFLAMMATION; RESISTANCE; TH1;

D O I：

10.3389/fimmu.2022.875412

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

CD44 partcipates in multiple inflammatory reactions. Here, we aimed to investigate the role of CD44 and the ligand, hyaluronan (HA), on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) pathogenesis. We found that CD44 was universally expressed in CD4(+) lymphocytes in the peripheral blood of CP/CPPS patients. After silencing CD44 expression or delivering 4-methylumbelliferone (4-MU), the pain severity and prostatic inflammation were significantly relieved. In vitro assay found that HA/CD44 was able to regulate T helper 1 (Th1) cells differentiation, the deficiency of which diminished experimental autoimmune prostatitis (EAP) susceptibility. Bioinformatic analysis suggested that after HA or 4-MU treatment, mTOR signaling was significantly altered, and these results were confirmed by subsequent Western blotting assay. Besides, mass spectrometry and co-immunoprecipitation assays found that CD44 was able to interact with Annexin A1 (ANX A1), and this kind of interaction stabilized ANX A1 protein and maintained the activation of Akt/mTOR pathway. Meanwhile, HA-treatment-enhanced prostatic inflammation, Th1 cell differentiation, and Akt/mTOR pathway activation were reversed after silencing the expression of ANX A1 using shANX A1-lentivirus. The present study systematically investigates the functional role of HA/CD44 in CP/CPPS and identifies novel mechanisms for HA/CD44 promoting Th1 cell differentiation. Targeting the HA/CD44/ANX A1/Akt/mTOR signaling represents novel potential therapeutic strategies for patients with CP/CPPS.

引用

页数：12

共 27 条

[1] Antibodies to CD44 and integrin α4, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment [J].