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작성자 : 관리자 날짜 : 작성일15-10-15 23:08 조회 : 3,601회본문
제 499 회 생명과학연구소 세미나 2015.10.15 |
Novel miRNA mediated regulatory axis regulating T follicular helper cell (TFH) generation and function
강승구 교수 (강원대학교)
T cell help is essential for humoral immunity. A distinct CD4+ effector T cell subset, T follicular helper cells (TFH), provides this help to B cells. However, molecular mechanisms underlying TFH differentiation are still largely unknown. The mice with T cell-specific deletion of miR-17~92 or miR-155 miRNAs (KO mice) exhibited severely compromised TFH differentiation, germinal center formation, and antibody responses upon protein antigen immunization. miR-17~92 deficiency impairs T cell migration into B cell follicles, a defining feature of the TFH differentiation program and loss of miR-155 in T cells led to decreased in vivo proliferation and reduced CD40L expression of antigen-specific CD4+ T cells. Mechanistically, miR-17~92 family miRNAs limit the protein concentration of Phlpp2, thus exaggerated and prolonged expression of Phlpp2 protein compromises ICOS-induced PI3K signaling and impairs T cell migration into B cell follicles. miR-155 repressed the expression of Peli1, a ubiquitin ligase that degrades the NF-B family transcription factor c-Rel, which controls cellular proliferation and CD40L expression. Collectively, my study revealed novel regulatory axis of TFH cell differentiation and functions controlled by miRNAs..
Education & Research Experiences
1993 – 1997: B.S., Yonsei University, Biology
1997 – 2000: M.S., Yonsei University, Molecular Immunology
2003 – 2009: Ph.D., Purdue University, Immunology and Microbiology
2009 – 2010: Postdoctoral Fellow, Purdue University, IN
2010 – 2015: Research Associate, The Scripps Research Institute, CA
2015 – Current: Assistant Professor, Kangwon National University, Korea
Papers
Kang SG*, Liu W*, Lu P*,Jin HY, Lim HW, Shepherd J, Fremgen D, Verdin E, Qi H, Oldstone M, Teijaro J, Xiao C. miR-17~92 family microRNAs are critical regulators of T follicular helper cell differentiation. Nature Immunology. 2013,14,849-57 외 15편
