FY2020 Annual Report

Immune Signal Unit
Associate Professor Hiroki Ishikawa

Abstract

Research in our unit has focused on molecular mechanisms of differentiation of immune cells. We are particularly interested in transcriptional regulatory mechanisms of T cell differentiation. Our recent data demonstrate important roles for the AP-1 transcription factor JunB in the functional diversification of T cell subsets. In this fiscal year, we investigated JunB-dependent transcriptional regulatory mechanisms in various CD4 effector T cell differentiation. We have also started a project for COVID-19 immunity with researchers in Naha Medical Association.

1. Staff

Dr. Hiroki Ishikawa, Associate Professor
Dr. Daiki Sasaki, Postdoctoral Scholar
Dr. Naoyuki Taira, Postdoctoral Scholar
Dr. Rajkumar Singh, Staff Scientist
Dr. Miho Tamai, Staff Scientist
Ms. Mio Miyagi, Research Unit Technician
Mr. Yu Seto, Research Unit Technician
Ms. Sakura Toguchi, Research Assistant
Mr. Tsung-Han Hsieh, Student
Ms. Shukla Sarker, Student
Mr. Ke Wang, Student
Mr. Tsung-Yen Huang, Student
Ms. Hsiao-Chiao Hsieh, Student
Mr. Charles Whitaker, Student
Ms. Mi Yang, Student
Mr. Masato Hirota, Student
Ms. Gulfiya Kadyrzhanova, Student
Ms. Sachie Yukawa, Student
Ms. Rika Yoshizawa, Research Unit Administrator

2. Collaborations

Analysis of immune responses against SARS-CoV-2 in Okinawan donors.

Type of collaboration: Joint research
Researchers: Dr. Mitsuo Kina (Kina Clinic), Dr. Osamu Tamai (Akebono Clinic), Dr. Kentaro Tamaki (Naha-nishi Clinic), Dr. Hiroaki Tomori (Yaesu Clinic), Dr. Masatake Miyagi (Arakawa Clinic), Dr. Chiaki Yamashiro (Yamashiro Orthopedic Surgery Ophthalmology Clinic), Dr. Eishin Sakihara (Lifestyle Related Disease Medical Center, Naha Medical Association)

3. Activities and Findings

IRF4 is critical for differentiation of various CD4+ effector T cells, such as T helper 1 (Th1), Th2, and Th17 subsets, through interaction with BATF-containing AP-1 heterodimers. A major BATF heterodimeric partner, JunB, regulates Th17 differentiation, but the role of JunB in other CD4+ effector T subsets is not fully understood. In FY2020, we have demonstrated that JunB is essential for accumulation of Th1 and Th2 cells, as well as Th17 cells, both in vitro and in vivo. In mice immunized with lipopolysaccharide (LPS), papain, or complete Freund’s adjuvant (CFA), that induce predominantly Th1, Th2 and Th17 cells, respectively, accumulation of antigen-primed, Junb-deficient CD4+ T cells is significantly impaired. Loss of JunB decreases viability of cells activated under Th1-, Th2-, and Th17-polarizing conditions. RNA-sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) reveal that JunB directly regulates expression of various genes that are commonly induced in priming of na?ve CD4+ T cells, including a pro-apoptotic gene Bcl2l11 (encoding Bim), and genes that are specifically induced in Th1, Th2, and Th17 cells. Furthermore, JunB colocalizes with BATF and IRF4 at genomic regions for approximately half of JunB direct target genes. Taken together, JunB, in collaboration with BATF and IRF4, serves a critical function in differentiation of diverse CD4+ T cells by controlling common and lineage-specific gene expression.

In October, 2021, we have initiated a collaboration research with researchers in Naha Medical Association in order to measure immune responses against SARS-CoV-2 in Okinawan donors. We found that a substantial proportion of the donors have acquired SARS-CoV-2-specific T cell responses but not antibody responses. We will continue to characterize those pre-existing T cell responses in the next fiscal year.

FY2020 Annual Report

Abstract

1. Staff

2. Collaborations

Analysis of immune responses against SARS-CoV-2 in Okinawan donors.

3. Activities and Findings

4. Publications

4.1 Journals

4.2 Books and other one-time publications

4.3 Oral and Poster Presentations

5. Intellectual Property Rights and Other Specific Achievements

6. Meetings and Events

7. Other