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• W4313254210 endingPage "102843" @default.
• W4313254210 startingPage "102843" @default.
• W4313254210 abstract "Transforming growth factor-β1 (TGF-β1) can suppress the activation, proliferation, and function of many T-cell subsets, protecting organisms from inflammatory and autoimmune disease caused by an overexuberant immune response. However, whether and how TGF-β1 regulates T-cell immunity in early vertebrates remain unknown. Here, using a Nile tilapia (Oreochromis niloticus) model, we investigated suppression of the T-cell response by TGF-β1 in teleost species. Tilapia encodes an evolutionarily conserved TGF-β1, the expression of which in lymphocytes is significantly induced during the immune response following Edwardsiella piscicida infection. Once activated, tilapia T cells increase TGF-β1 production, which in turn suppresses proinflammatory cytokine expression and inhibits T-cell activation. Notably, we found administration of TGF-β1 cripples the proliferation of tilapia T cells, reduces the potential capacity of Th1/2 differentiation, and impairs the cytotoxic function, rendering the fish more vulnerable to bacterial infection. Mechanistically, TGF-β1 initiates the TGF-βR/Smad signaling pathway and triggers the phosphorylation and nuclear translocation of Smad2/3. Smad3 subsequently interacts with several transcriptional partners to repress transcription of cytokines IL-2 and IFN-γ but promote transcription of immune checkpoint regulator CTLA4 and transcription factor Foxp3. Furthermore, TGF-β1/Smad signaling further utilizes Foxp3 to achieve the cascade regulation of these T-cell genes. Taken together, our findings reveal a detailed mechanism by which TGF-β1 suppresses the T cell-based immunity in Nile tilapia and support the notion that TGF-β1 had already been employed to inhibit the T-cell response early in vertebrate evolution, thus providing novel insights into the evolution of the adaptive immune system." @default.
• W4313254210 created "2023-01-06" @default.
• W4313254210 creator A5007485175 @default.
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• W4313254210 creator A5087210747 @default.
• W4313254210 creator A5087811945 @default.
• W4313254210 creator A5089476014 @default.
• W4313254210 creator A5090061071 @default.
• W4313254210 date "2023-02-01" @default.
• W4313254210 modified "2023-09-27" @default.
• W4313254210 title "TGF-β1 suppresses the T-cell response in teleost fish by initiating Smad3- and Foxp3-mediated transcriptional networks" @default.
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• W4313254210 doi "https://doi.org/10.1016/j.jbc.2022.102843" @default.
• W4313254210 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36581209" @default.
• W4313254210 hasPublicationYear "2023" @default.
• W4313254210 type Work @default.
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• W4313254210 hasAuthorship W4313254210A5007485175 @default.
• W4313254210 hasAuthorship W4313254210A5015677261 @default.

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