Essential Roles of TIM-1 and TIM-4 Homologs in Adaptive Humoral Immunity in a Zebrafish Model

The Journal of Immunology : Official Journal of the American Association of Immunologists
Xiao-Gang XuJian-Zhong Shao

Abstract

TIM-1 and TIM-4 proteins have become increasingly attractive for their critical functions in immune modulation, particularly in CD4(+) Th2 cell activation. Thus, these proteins were hypothesized to regulate adaptive humoral immunity. However, further evidence is needed to validate this hypothesis. This study describes the molecular and functional characteristics of TIM-1 and TIM-4 homologs from a zebrafish (Danio rerio) model (D. rerio TIM [DrTIM]-1 and DrTIM-4). DrTIM-1 and DrTIM-4 were predominantly expressed in CD4(+) T cells and MHC class II(+) APCs under the induction of Ag stimulation. Blockade or knockdown of both DrTIM-1 and DrTIM-4 significantly decreased Ag-specific CD4(+) T cell activation, B cell proliferation, Ab production, and vaccinated immunoprotection against bacterial infection. This result suggests that DrTIM-1 and DrTIM-4 serve as costimulatory molecules required for the full activation of adaptive humoral immunity. DrTIM-1 was detected to be a trafficking protein located in the cytoplasm of CD4(+) T cells. It can translocate onto the cell surface under stimulation by TIM-4-expressing APCs, which might be a precise regulatory strategy for CD4(+) T cells to avoid self-activation before APCs stimulation. Furt...Continue Reading

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Citations

Mar 10, 2020·Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution·Hao ShenHaobin Zhao
Apr 15, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhi-Fei LiuJian-Zhong Shao
Aug 29, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jiang-Yuan LiJian-Zhong Shao
Jun 27, 2019·PLoS Neglected Tropical Diseases·Bethany BruntonWendy Maury
Apr 17, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jian-Fei JiJian-Zhong Shao
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Kelly Z MiaoHui Feng

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