FOXP3型
T细胞受体
CD28
磷酸化
受体
转化生长因子
乳铁蛋白
细胞生物学
信号转导
生物
化学
分子生物学
免疫学
T细胞
免疫系统
生物化学
作者
Young‐Saeng Jang,Seok‐Won Yang,Tae‐Gyu Kim,Ha‐Eon Song,Sunhee Park,Eun Hye Lee,Seung Goo Kang,Sung‐il Yoon,Hyun–Jeong Ko,Geun‐Shik Lee,Seok‐Rae Park,Su Ryeon Seo,Pyeung‐Hyeun Kim
出处
期刊:Immunology
[Wiley]
日期:2022-08-30
卷期号:168 (1): 110-119
摘要
We recently reported that lactoferrin (LF) induces Foxp3+ Treg differentiation through binding to TGFβ receptor III (TβRIII), and this activity was further enhanced by TGFβ1. Generally, a low T-cell receptor (TCR) signal strength is favourable for Foxp3+ Treg differentiation. In the present study, we explored the effect of lactoferrin chimera (LFch, containing lactoferricin [aa 17-30] and lactoferrampin [aa 265-284]), along with TGFβ1 on Foxp3+ Treg differentiation. LFch alone did not induce Foxp3 expression, yet LFch dramatically enhanced TGFβ1-induced Foxp3 expression. LFch had little effect on the phosphorylation of Smad3, a canonical transcriptional factor of TGFβ1. Instead, LFch attenuated the phosphorylation of S6 (a target of mTOR), IκB and PI3K. These activities of LFch were completely abrogated by pretreatment of LFch with soluble TGFβ1 receptor III (sTβRIII). Consistent with this, the activity of LFch on TGFβ1-induced Foxp3 expression was also abrogated by treatment with sTβRIII. Finally, the TGFβ1/LFch-induced T cell population substantially suppressed the proliferation of responder CD4+ T cells. These results indicate that LFch robustly enhances TGFβ1-induced Foxp3+ Treg differentiation by diminishing TCR/CD28 signal intensity.
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