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

Daiki Karigane; Miho Haraguchi; Noriko Toyama-Sorimachi; Emi K Nishimura; Keiyo Takubo

doi:10.1016/j.bbrc.2022.01.091

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

Biochem Biophys Res Commun. 2022 Mar 12:596:29-35. doi: 10.1016/j.bbrc.2022.01.091. Epub 2022 Jan 26.

Authors

Daiki Karigane¹, Miho Haraguchi², Noriko Toyama-Sorimachi³, Emi K Nishimura⁴, Keiyo Takubo⁵

Affiliations

¹ Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan; Research Fellow of Japan Society for the Promotion of Science, Japan. Electronic address: karigane@hotmail.com.
² Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
³ Department of Molecular Immunology and Inflammation, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
⁴ Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; Division of Aging and Regeneration, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
⁵ Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. Electronic address: keiyot@gmail.com.

PMID: 35108651
DOI: 10.1016/j.bbrc.2022.01.091

Abstract

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 (Mitf) 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.

Keywords: Mitf; T cell differentiation; Thymic dendritic cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Marrow Cells / immunology
Bone Marrow Cells / metabolism
Cell Differentiation / genetics
Cell Differentiation / immunology*
Cells, Cultured
Dendritic Cells / immunology*
Dendritic Cells / metabolism
Flow Cytometry
Gene Expression Regulation / immunology
Hyperplasia
Integrin alpha4 / genetics
Integrin alpha4 / immunology
Integrin alpha4 / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Microphthalmia-Associated Transcription Factor / genetics
Microphthalmia-Associated Transcription Factor / immunology*
Microphthalmia-Associated Transcription Factor / metabolism
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes / immunology*
T-Lymphocytes / metabolism
Thymus Gland / immunology*
Thymus Gland / metabolism
Thymus Gland / pathology

Substances

Microphthalmia-Associated Transcription Factor
Mitf protein, mouse
Integrin alpha4