Effects of estrogen signaling on T cell recruitment and polarization in inflamed skeletal muscle with acute myoinjury
10.16098/j.issn.0529-1356.2025.06.008
- VernacularTitle:雌激素信号调控急性损伤骨骼肌内T细胞募集与极化
- Author:
Zi-Wei ZHAO
1
;
Xiao-Ting JIAN
;
Jun-Yi XIE
;
Jing-Wen HUANG
;
Yang-Yang LI
;
Qi-Sen WANG
;
Zhao-Hong LIAO
;
Hua LIAO
Author Information
1. 广东省组织构建与检测重点实验室,南方医科大学基础医学院解剖学教研室,广州 510515
- Keywords:
Estrogen;
Myoinjury;
T cell;
Ovariectomy;
Enzyme-linked immunosorbent assay;
Mouse
- From:
Acta Anatomica Sinica
2025;56(6):688-696
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of estrogen signaling on T-cell recruitment and polarization in acutely injured skeletal muscle.Methods One hundred C57BL/6 male mice,one hundred and eighty C57BL/6 female mice were selected.Twenty-five female mice were ovariectomized(OVX)and 10 male mice were taken as the sham-operated(sham).Then,cardiotoxin(CTX)induced tibialis anterior(TA)injury for preparing mice myoinjury model.Subcutaneous injection of 17β-estradiol(E2)or estrogen receptor antagonist 4-hydroxytamoxifen(4-OHT)was performed.A total of 140 mice(70 males and 70 females)were divided into four group including:PBS-male,CTX-male,PBS-female,and CTX-female.Serum estradiol(E2)levels were measured by ELISA,and muscle injury models were validated via HE staining.Subsequently,20 male and 20 female mice were selected for immunofluorescence(IF)and Real-time PCR to assess estrogen receptors(ER)expression in injured muscle tissue.Further,10 male and 40 female mice were allocated into five experimental groups,including CTX,CTX+E2,CTX+4-OHT,CTX+OVX,CTX+sham.HE staining and IF were performed to evaluate inflammatory infiltration in the injured muscle.Additionally,50 female mice were divided into CTX and CTX+OVX groups,and IF combined with flow cytometry were used to analyze T-cell phenotypes and muscle fiber regeneration in the injured muscle.Results In vivo,serum E2 and myofiber ERβ increased post-injury in mice of both sexes,significantly higher in females.Compared to the control group,E2 alleviated inflammation,OVX exacerbated inflammation,increased CD4+T-cell infiltration,elevated T helper 1 cell(Th1)response,decreased regulatory T cells(Tregs),impaired regeneration.In vitro,IFN-γ/LPS significantly upregulated ERβ in myotubes.Conclusion Estrogen signaling critically regulates muscle inflammation.Estrogen deficiency(OVX)delays repair of skeletal muscle by promoting Th1 response and suppressing Tregs function.
