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Cited by 7T-cell and B-cell ImmunologyRheumatoid Arthritis Research and TherapiesSystemic Lupus Erythematosus Research

Tespa1 Deficiency Dampens Thymus-Dependent B-Cell Activation and Attenuates Collagen-Induced Arthritis in Mice

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Yao, Yunliang, Huang, Wei, Li, Xiaoyu, Li, Xiawei, Qian, Jin, Han, Hui, Sun, Hui, An, Xiangli +2 more·2018·Frontiers in Immunology
DOI 10.3389/fimmu.2018.00965PMC PMC5960706
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Abstract

Thymocyte-expressed, positive selection-associated 1 (Tespa1) plays an important role in both T cell receptor (TCR)-driven thymocyte development and in the FcεRI-mediated activation of mast cells. Herein, we show that lack of Tespa1 does not impair B cell development but dampens the in vitro activation and proliferation of B cells induced by T cell-dependent (TD) antigens, significantly reduces serum antibody concentrations in vivo and impairs germinal center formation in both aged and TD antigen-immunized mice. We also provide evidence that dysregulated signaling in Tespa1-deficient B cells may be linked to CD40-induced TRAF6 degradation, and subsequent effects on 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2 (PLCγ2) phosphorylation, MAPK activation, and calcium influx. Furthermore, we demonstrate that Tespa1 plays a critical role in pathogenic B cells, since Tespa1-deficient chimeric mice showed a lower incidence and clinical disease severity of collagen-induced arthritis. Overall, our study demonstrates that Tespa1 is essential for T cell-dependent B cell responses, and suggests an important role for Tespa1 during the development of autoimmune arthritis.

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  • Pathogenic B cells which form in thymocyte-expressed, positive selection-associated 1 KO mice in a collagen-induced arthritis model were impaired in PLCγ2 function and associated calcium flux, thereby reducing the severity of their disease compared with control mice.

    “Pathogenic B cells which form in the thymocyte-expressed, positive selection–associated 1 KO mice in a collagen-induced arthritis model were impaired in PLCγ2 function, and associated calcium flux, thereby reducing the severity of their disease in comparison with control mice (117).”

    From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [117]

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  • Thymocyte-expressed, positive selection-associated 1 is critical in thymic T cell development and activation of mast cells via FcεRI, and is important to B cell functions including proliferation, activation, germinal center formation, and serum antibody production.

    “Thymocyte-expressed, positive selection–associated 1 is critical in thymic T cell development and activation of mast cells via FcεRI, as well as being of importance to B cell functions including proliferation, activation, germinal center formation, and serum antibody production (117).”

    From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [117]

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Cited by

Sorted by citations

Authors
Yao, Y., Huang, W., Li, X., Li, X., Qian, J., Han, H., Sun, H., An, X., Lu, L., & Zhao, H.
Affiliations
  • Huzhou Normal University (CN)
  • Children's Hospital of Zhejiang University (CN)
  • Zhejiang University (CN)
Corresponding author
Zhao, Hongxing
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2018-05-14
Volume
9
Pages
965-965
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2018.00965
PMC
PMC5960706
OpenAlex
W2800769724
Cited by
7
References
4
Citations by year
2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2019: 1
FWCI
0.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Youth Foundation of China (31300733)
  • Natural Science Foundation of Zhejiang Province (LY18C080001, Q16C080002)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
Keywords
B cell activation, T cell-dependent B cell response, germinal center formation, collagen-induced arthritis, autoimmunity, CD40 signaling, MAPK activation, calcium influx, chimeric mice, antibody production
MeSH terms
Animals, Arthritis, Experimental, B-Lymphocytes, Calcium, Collagen, Lymphocyte Activation, Mice, Inbred C57BL, Phosphorylation, T-Lymphocytes, Signal Transduction, Autoimmunity, Mice, Knockout, Germinal Center, CD40 Antigens, TNF Receptor-Associated Factor 6, Adaptor Proteins, Signal Transducing, Mice, Phospholipase C gamma

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