A role of Achaete-scute complex homolog 2 in T follicular regulatory cell development

Kazuma Iida; Kensuke Suga; Kotaro Suzuki; Shunjiro Kurihara; Yoko Yabe; Takahiro Kageyama; Kazuyuki Meguro; Shigeru Tanaka; Arifumi Iwata; Akira Suto; Hiroshi Nakajima

doi:10.1016/j.bbrc.2023.04.065

A role of Achaete-scute complex homolog 2 in T follicular regulatory cell development

Biochem Biophys Res Commun. 2023 Jul 5:664:9-19. doi: 10.1016/j.bbrc.2023.04.065. Epub 2023 Apr 22.

Authors

Kazuma Iida¹, Kensuke Suga², Kotaro Suzuki³, Shunjiro Kurihara⁴, Yoko Yabe⁵, Takahiro Kageyama⁶, Kazuyuki Meguro⁷, Shigeru Tanaka⁸, Arifumi Iwata⁹, Akira Suto¹⁰, Hiroshi Nakajima¹¹

Affiliations

¹ Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan. Electronic address: diaspray@gmail.com.
² Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan. Electronic address: k-suga@chiba-u.jp.
³ Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan. Electronic address: suzuki_k@faculty.chiba-u.jp.
⁴ Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan. Electronic address: s.kurihara84@chiba-u.jp.
⁵ Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan. Electronic address: yyabe@chiba-u.jp.
⁶ Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan. Electronic address: t.kageyama@chiba-u.jp.
⁷ Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan. Electronic address: kazuyuki.meguro@chiba-u.jp.
⁸ Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan. Electronic address: stanaka@chiba-u.jp.
⁹ Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan. Electronic address: aiwata@chiba-u.jp.
¹⁰ Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan. Electronic address: suaki@faculty.chiba-u.jp.
¹¹ Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba, 260-8670, Japan; Chiba University Synergy Institute for Futuristic Mucosal Vaccine Research and Development (cSIMVa), Chiba, Japan. Electronic address: nakajimh@faculty.chiba-u.jp.

PMID: 37130460
DOI: 10.1016/j.bbrc.2023.04.065

Abstract

T follicular regulatory (Tfr) cells, a subset of CD4⁺ Foxp3⁺ regulatory T (Treg) cells, locate to the lymphoid follicle and germinal center (GC) and regulate antibody responses. Tfr cells express the functional molecules of follicular helper T (Tfh) cells, including CXCR5 and Bcl6. CD25^- mature Tfr cells differentiate from CD25⁺ Treg cells through CD25⁺ immature Tfr cells. Others and we have shown that Achaete-scute complex homolog 2 (Ascl2) plays a role in Tfh cell development; however, the role of Ascl2 in the development of Tfr cells remains unclear. Here, we found that Ascl2 was highly and preferentially expressed in CD25⁺ Tfr cells and CD25^- Tfr cells, and that the differentiation from CD25⁺ Tfr cells to CD25^- Tfr cells was impaired by the absence of Ascl2. Furthermore, the forced Ascl2 expression in Treg cells downregulated CD25 expression and suppressed IL-2-induced phosphorylation of STAT5, which is known to suppress CD25^- Tfr cell development. Finally, we found that the downregulation of CD25 by Ascl2 in Treg cells is independent of Bach2, which also regulates CD25 downregulation in CD25⁺ Tfr cells. These results suggest that Ascl2 plays a vital role in developing Tfr cells, possibly by downregulating CD25 expression in a Bach2-independent mechanism.

Keywords: Achaete-scute complex homolog 2; CD25; Foxp3; T follicular regulatory cell.

Publication types

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

MeSH terms

Animals
Basic-Leucine Zipper Transcription Factors / metabolism
Cell Differentiation
Germinal Center
Mice
T-Lymphocytes, Helper-Inducer*
T-Lymphocytes, Regulatory*

Substances

Basic-Leucine Zipper Transcription Factors