TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization.
10.1007/s12264-023-01094-x
- Author:
Siying QU
1
;
Shengfeng HU
2
;
Huiting XU
1
;
Yongjian WU
1
;
Siqi MING
1
;
Xiaoxia ZHAN
3
;
Cheng WANG
4
;
Xi HUANG
5
Author Information
1. Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China.
2. The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China.
3. Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
4. Division of Nephrology, Department of Medicine, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China.
5. Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China. huangxi6@mail.sysu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Experimental autoimmune encephalomyelitis;
Multiple sclerosis;
T helper 17;
Triggering receptor expressed on myeloid cells 2
- MeSH:
Animals;
Humans;
Mice;
CD4-Positive T-Lymphocytes/pathology*;
Cell Differentiation;
Encephalomyelitis, Autoimmune, Experimental/metabolism*;
Mice, Inbred C57BL;
Multiple Sclerosis;
Th1 Cells/pathology*
- From:
Neuroscience Bulletin
2024;40(1):17-34
- CountryChina
- Language:English
-
Abstract:
Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4+ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4+ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
