Institute for Frontier Life and Medical Sciences, Kyoto University

A new mechanism of regulatory T cell generation to suppress excessive immune responses ―Non-coding DNA sequences indispensable for immune tolerance were discoveredー

Ryoji Kawakami,1,3 Yohko Kitagawa,1,3 Kelvin Y. Chen,3 Masaya Arai,3 Daiya Ohara,2 Yamami Nakamura,3 Keiko Yasuda,1,3 Motonao Osaki,1,3 Norihisa Mikami,1,3 Caleb A. Lareau,4 Hitomi Watanabe,2 Gen Kondoh,2 Keiji Hirota,2 Naganari Ohkura,3 and Shimon Sakaguchi1,3

(1 Department of Experimental Pathology, Institute for Frontier Life and Medical Sciences, Kyoto University, 2 Laboratory of Integrative Biological Science, Institute for Frontier Life and Medical Sciences, Kyoto University, 3 Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, 4 Departments of Genetics and Pathology, Stanford University)

Distinct Foxp3 enhancer elements coordinate development, maintenance and function of regulatory T cells

Immunity (2021) doi.org/10.1016/j.immuni.2021.04.005

Abstract

Prof. Sakaguchi’s and Prof. Kondoh’s team identified non-coding DNA sequences indispensable for regulatory T cell (Treg) generation. These DNA sequences are distributed into the two separated regions near the Foxp3 gene locus, the master transcription factor of Tregs. Defect of these elements developed severe autoimmune-diseases. Controlling the development and function of Tregs holds promise for the new therapies for immunological diseases. This work is a collaboration study with Osaka university and Stanford university.

See also the press release from Osaka univ.

http://www.ifrec.osaka-u.ac.jp/en/research/20210506-1000.htm

Figure. Non-coding DNA elements, CNS0 and CNS3 regions on chromosome X, control the expression of Foxp3 gene to maintain immune tolerance.