Session Type: Poster Session (Tuesday)
Session Time: 9:00AM-11:00AM
Background/Purpose: T follicular helper cells (Tfh cells) are a newly discovered subset of CD4+ T cells, which play a mainly role in inducing B cells to produce antibody. Tfh cells are over activated in systemic lupus erythematosus (SLE) patients, consequently bring about immune damages. Hematopoietic progenitor kinase 1 (HPK1) can inhibit T cell-mediated immune responses, but the role that HPK1 plays in Tfh cells from SLE patients remain elusive. The aim of this study is to investigate whether HPK1 plays roles in SLE Tfh cells.
Methods: Naïve CD4+ T cells and B cells were isolated from healthy controls and SLE patients. Then Naïve CD4+ T cells were induced to differentiate into Tfh cells by stimulating with anti-CD3 antibody, anti-CD28 antibody, IL-6, IL-12, IL-21, and TGF-β. HPK1 mRNA and protein levels in Tfh cells were determined by real-time RT-PCR and western blotting. Detection of IL-21, CXCL13, IFNγ, IL-17A, IgM, IgG1, IgG2a, IgG2b and IgG3 levels were performed by ELISA. Tfh cells proliferations were analyzed with MTT assay.
Results: We identified HPK1 mRNA and protein levels were significantly decreased in Tfh cells from patients with SLE. Moreover, HPK1 mRNA levels were found to negatively correlated with SLE disease activity as measured by SLE Disease Activity Index (SLEDAI). Down-regulation of HPK1 in healthy Tfh cells significantly accelerated Tfh cells proliferation and productions of IL-21, CXCL13, IFNγ, IgG1, IgG2a, IgG2b, and IgG3. There were no marked changes in IL-17A and IgM amounts. Consistent with these findings, overexpressing HPK1 in SLE Tfh cells caused significant decrease in Tfh cells proliferation and productions of IL-21, CXCL13, IFNγ, IgG1, IgG2a, IgG2b, and IgG3. And there were no significant alters in IL-17A and IgM levels.
Conclusion: Our results show for the first time that inhibited expression of HPK1 in SLE Tfh cells contributes to Tfh cells overactivation and B cells overstimulation, which lead to the development of SLE at last.
To cite this abstract in AMA style:Zhang Q, Zhang H. Inhibited Expression of Hematopoietic Progenitor Kinase 1 in Tfh Cells Contributes to Autoimmunity in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/inhibited-expression-of-hematopoietic-progenitor-kinase-1-in-tfh-cells-contributes-to-autoimmunity-in-systemic-lupus-erythematosus/. Accessed September 24, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/inhibited-expression-of-hematopoietic-progenitor-kinase-1-in-tfh-cells-contributes-to-autoimmunity-in-systemic-lupus-erythematosus/