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KMID : 0923620230230050037
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Immune Network
2023 Volume.23 No. 5 p.37 ~ p.37
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Combined Treatment With TGF-β1, Retinoic Acid, and Lactoferrin Robustly Generate Inducible Tregs (iTregs) Against High Affinity Ligand
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Jang Young-Saeng
Park Sun-Hee
Kang Seung-Goo
Lee Jung-Shin
Ko Hyun-Jeong
Kim Pyeung-Hyeun
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Abstract
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Forkhead box P3-positive (Foxp3+)-inducible Tregs (iTregs) are readily generated by TGF-β1 at low TCR signaling intensity. TGF-β1?mediated Foxp3 expression is further enhanced by retinoic acid (RA) and lactoferrin (LF). However, the intensity of TCR signaling required for induction of Foxp3 expression by TGF-β1 in combination with RA and LF is unknown. Here, we found that either RA or LF alone decreased TGF-β1?mediated Foxp3 expression at low TCR signaling intensity. In contrast, at high TCR signaling intensity, the addition of either RA or LF strongly increased TGF-β1?mediated Foxp3 expression. Moreover, decreased CD28 stimulation was more favorable for TGF-β1/LF?mediated Foxp3 expression. Lastly, we found that at high signaling intensities of both TCR and CD28, combined treatment with TGF-β1, RA, and LF induced robust expression of Foxp3, in parallel with powerful suppressive activity against responder T cell proliferation. Our findings that TGFβ/RA/LF strongly generate high affinity Ag-specific iTreg population would be useful for the control of unwanted hypersensitive immune reactions such as various autoimmune diseases.
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KEYWORD
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Lactoferrin, Transforming growth factor beta, Retinoic acid, Regulatory T cells, forkhead box P3 protein, T cell receptor, CD28 antigen
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