Mitf is required for T cell maturation by regulating dendritic cell homing to the thymus

被引:1
作者
Karigane, Daiki [1 ,5 ]
Haraguchi, Miho [1 ]
Toyama-Sorimachi, Noriko [2 ]
Nishimura, Emi K. [3 ,4 ]
Takubo, Keiyo [1 ]
机构
[1] Natl Ctr Global Hlth & Med, Res Inst, Dept Stem Cell Biol, Tokyo 1628655, Japan
[2] Natl Ctr Global Hlth & Med, Res Inst, Dept Mol Immunol & Inflammat, Tokyo, Japan
[3] Tokyo Med & Dent Univ, Med Res Inst, Dept Stem Cell Biol, Tokyo, Japan
[4] Univ Tokyo, Inst Med Sci, Div Aging & Regenerat, Tokyo, Japan
[5] Japan Soc Promot Sci, Tokyo, Japan
关键词
Thymic dendritic cell; T cell differentiation; Mitf; MAST-CELLS; MICROPHTHALMIA; EXPRESSION; STEM; THYMOCYTES; SELECTION; HAIR;
D O I
10.1016/j.bbrc.2022.01.091
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Thymic dendritic cells (DCs) promote immune tolerance by regulating negative selection of autoreactive T cells in the thymus. How DC homing to the thymus is transcriptionally regulated is still unclear. Microphthalmia-associated transcription factor (Mill) is broadly expressed and plays essential roles in the hematopoietic system. Here, we used Mitf-mutated mice (Mitf(Vit/Vit)) and found enlargement of the thymus and expansion of CD4/CD8 double-positive T cells. Mitf was highly expressed in a subset of thymic DCs among the hematopoietic system. Genetic mutation or pharmacological inhibition of Mitf in DCs decreased the expression levels of Itga4, which are critical molecules for the homing of DCs to the thymus. Further, inhibition of Mitf decreased thymic DC number. These results suggest a pivotal role of Mitf in the maintenance of T cell differentiation by regulating the homing of DC subsets within the thymus. (C) 2022 Elsevier Inc. All rights reserved.
引用
收藏
页码:29 / 35
页数:7
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