Abstract
Sjögren’s syndrome (SjS) is a systemic autoimmune disease marked by xerostomia (dry mouth), keratoconjunctivitis sicca (eye dryness), and other systematic disorders. Its pathogenesis involves an inflammatory process that is characterized by lymphocytic infiltration into exocrine glands and other tissues. Although the development of ectopic lymphoid tissue and overproduction of autoantibodies by hyperactive B cells suggest that they may promote SjS development, treatment directed towards them fails to induce significant laboratory or clinical improvement. T cells are overwhelming infiltrators in most phases of the disease, and the involvement of multiple T cell subsets of suggests the extraordinary complexity of SjS pathogenesis. The factors, including various cellular subtypes and molecules, regulate the activation and suppression of T cells. T cell activation induces inflammatory cell infiltration, B cell activation, tissue damage, and metabolic changes in SjS. Knowledge of the pathways that link these T cell subtypes and regulation of their activities are not completely understood. This review comprehensively summarizes the research progress and our understanding of T cells in SjS, including CD4+ T cells, CD8+ TRM cells, and innate T cells, to provide insights into for clinical treatment.
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Abbreviations
- APCs:
-
Antigen-presenting cells
- AQP:
-
Aquaporin
- BAFF:
-
B cell activating factor
- Cat S:
-
Cathepsin S
- cTfh:
-
Circulating follicular helper T cell
- cTfr:
-
Circulating follicular regulatory T cell
- CCL:
-
Chemokine (C-C motif) ligand
- CXCL:
-
Chemokine (C-X-C motif) ligand
- CCR:
-
CXC chemokine receptor
- CXCR:
-
CXC chemokine receptor
- DCs:
-
Dendritic cells
- DN T cells:
-
CD4&CD8 double-negative T cells
- EGMs:
-
Extraglandular manifestations
- ELS:
-
Ectopic lymphoid-like structures
- GC:
-
Germinal center
- GLS:
-
GC-like structures
- GWAS:
-
Genome-wide association studies
- LAMP:
-
Lysosome-associated membrane glycoprotein
- ICAM:
-
Intercellular adhesion molecule
- ICOS:
-
Inducible T cell co-stimulator
- ICOSL:
-
ICOS ligand
- IFN:
-
Interferon
- IFN-γR:
-
IFN-γ receptor
- IL:
-
Interleukin
- IL-22R:
-
IL-22 receptor
- iNKT cell:
-
Invariant natural killer T cell
- MAIT cell:
-
Mucosal-associated invariant T cell
- MDC:
-
Macrophage-derived chemokine
- MetS:
-
Metabolic syndrome
- MHC:
-
Major histocompatibility complex class
- MMP:
-
Matrix metalloproteinase
- NK:
-
Natural killer
- NOD:
-
Non-obese diabetic mouse
- pDCs:
-
Plasmacytoid DC cells
- ROR:
-
RAR-related orphan receptor
- SGEC:
-
Salivary gland epithelial cell
- SjS:
-
Sjögren’s syndrome
- SLE:
-
Systemic lupus erythematosus
- SLO:
-
Secondary lymphoid organs
- S1P:
-
Sphingosine 1-phosphate
- TARC:
-
Thymus and activation-regulated chemokine
- Tfh:
-
Follicular helper T cell
- Tfr:
-
Follicular regulatory T cell
- TGF-β:
-
Transforming growth factor beta
- Th:
-
Helper T cell
- TLRs:
-
Toll-like receptors
- TNF-α:
-
Tumor necrosis factor alpha
- Treg:
-
Regulatory T cell
- TRM:
-
Tissue resident memory T cell
- Tr1:
-
Type 1 regulatory T cell
- VCAM-1:
-
Vascular cell adhesion molecule-1.
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Authorship
Yuan Yao, Jin-Fen Ma, Ting Xu, and Cai-Yue Gao wrote the manuscript. Yuan Yao, JIn-Fen Ma, and Cai-Yue Gao designed and drew the figures; Christopher Chang, Patrick M. Eric Gershwin, and Zhe-Xiong Lian wrote and edited the manuscript.
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This work is supported by the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2017ZT07S054), the National Key R&D Program of China (2017YFA0205600), and the National Natural Science Foundation of China (81901653, 81701597).
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Yao, Y., Ma, JF., Chang, C. et al. Immunobiology of T Cells in Sjögren’s Syndrome. Clinic Rev Allerg Immunol 60, 111–131 (2021). https://doi.org/10.1007/s12016-020-08793-7
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DOI: https://doi.org/10.1007/s12016-020-08793-7