NFATC1とFOXP3タンパク質の減少による一般化白斑における末梢性調節性T細胞によるCD8とCD4 T細胞の抑制の減少

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Exp. Dermatol..2020 Jul;doi: 10.1111/exd.14157.Epub 2020-07-18.

NFATC1とFOXP3タンパク質の減少による一般化白斑における末梢性調節性T細胞によるCD8とCD4 T細胞の抑制の減少

Decreased suppression of CD8 and CD4 T cells by peripheral Regulatory T cells in Generalized Vitiligo due to reduced NFATC1 and FOXP3 proteins.

Prashant S Giri
Mitesh Dwivedi
Rasheedunnisa Begum

PMID: 32682346 DOI: 10.1111/exd.14157.

抄録

背景:

全身性白斑(GV)における活性化T細胞の抑制にはレギュラトリーT細胞(Tregs)が関与している。

BACKGROUND: Regulatory T cells (Tregs) are involved in suppression of activated T cells in generalized vitiligo(GV).

目的:

本研究は、GV患者55名と対照45名のTreg:CD8およびTreg:CD4 T細胞の共培養系におけるTregの機能的欠損を調べることを目的とした。

OBJECTIVES: The study was aimed to investigate Tregs functional defects in Treg:CD8 and Treg:CD4 T cells co-culture systems of 55 GV patients and 45 controls.

方法:

METHODS: CD8 and CD4 T cell proliferation was assessed by BrdU assay, production of IL-10, TGF-β & IFN-γ cytokines was assessed by ELISA and FOXP3, CD25, NFATC1 and CD44 proteins were measured by flow cytometry.

結果:

RESULTS: GV patients showed reduced suppression of CD8 & CD4 T cells(p=0.0384,p=0.0084), increased IFN-γ(p<0.0001,p=0.0019), decreased IL-10 & TGF-β(p<0.0001) and decreased FOXP3, CD25 & NFATC1 proteins(p<0.0001). Active vitiligo(AV) patients showed reduced suppression of CD8 & CD4 T cells(p=0.006,p=0.015), increased IFN-γ(p=0.036,p=0.045), decreased IL-10(p=0.009,p=0.021), FOXP3(p=0.0244) & NFATC1(p=0.019). Severe GV (50-75% VASI) patients showed reduced suppression of CD8 & CD4 T cells(p=0.0003,p=0.001), increased IFN-γ(p=0.0029,p<0.0001), decreased IL-10(p=0.0057,p=0.0017), FOXP3(p=0.002) & NFATC1(p=0.0347). VASI score was positively correlated with suppression of CD8 & CD4 T cells(p=0.0006,p<0.0001), IL-10(p=0.0096,p=0.029), FOXP3(p=0.0008) & NFATC1(p=0.043) whereas it was negatively correlated with IFN-γ(p=0.0029,p=0.0017). Early age of onset patients' Tregs demonstrated decreased suppression of CD8 & CD4 T cells(p=0.0156,p=0.0074), decreased TGF-β(p=0.0212,p=0.0083) and NFATC1(p=0.0103). NFATC1 was positively correlated with FOXP3 in Tregs(p<0.0001).

結論:

CONCLUSION: Our results suggest impaired Tregs suppressive function in GV patients due to decreased NFATC1, FOXP3, CD25, IL-10 & TGF-β resulting into increased CD8 and CD4 T cell proliferation and IFN-γ production. For the first time decreased NFATC1 levels were correlated with decreased FOXP3, thereby altering Treg cell function in GV patients. Additionally, decreased Treg cell function also affected onset, activity and severity of GV.