Details

Autor(en) / Beteiligte

• Jang, Young‐Saeng
• Yang, Seok‐Won
• Kim, Tae‐Gyu
• Song, Ha‐Eon
• Park, Sunhee
• Lee, Eun Hye
• Kang, Seung‐Goo
• Yoon, Sung‐il
• Ko, Hyun‐Jeong
• Lee, Geun‐Shik
• Park, Seok‐Rae
• Seo, Su Ryeon
• Kim, Pyeung‐Hyeun

Titel

Lactoferrin‐derived chimeric peptide (LFch) strongly boosts TGFβ1‐mediated inducible Treg differentiation possibly through downregulating TCR/CD28 signalling

Ist Teil von

• Immunology, 2023-01, Vol.168 (1), p.110-119

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2023

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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. We previously found that lactoferrin (LF) induces Foxp3+ Treg differentiation and synergized with TGFβ1. In the present study, we investigated the effect of lactoferrin chimera (LFch), mimicking the functional peptide domain of LF, along with TGFβ1 on Foxp3+ Treg differentiation. LFch remarkably enhances TGFβ1‐induced Foxp3+ Treg differentiation by diminishing TCR/CD28 signal intensity.