AUTHOR=Suzuki Akane S. , Yagi Ryoji , Kimura Motoko Y. , Iwamura Chiaki , Shinoda Kenta , Onodera Atsushi , Hirahara Kiyoshi , Tumes Damon J. , Koyama-Nasu Ryo , Iismaa Siiri E. , Graham Robert M. , Motohashi Shinichiro , Nakayama Toshinori 

TITLE=Essential Role for CD30-Transglutaminase 2 Axis in Memory Th1 and Th17 Cell Generation

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01536

DOI=10.3389/fimmu.2020.01536

ISSN=1664-3224

ABSTRACT=<p>Memory helper T (Th) cells are crucial for secondary immune responses against infectious microorganisms but also drive the pathogenesis of chronic inflammatory diseases. Therefore, it is of fundamental importance to understand how memory T cells are generated. However, the molecular mechanisms governing memory Th cell generation remain incompletely understood. Here, we identified CD30 as a molecule heterogeneously expressed on effector Th1 and Th17 cells, and CD30<sup>hi</sup> effector Th1 and Th17 cells preferentially generated memory Th1 and Th17 cells. We found that CD30 mediated signal induced Transglutaminase-2 (TG2) expression, and that the TG2 expression in effector Th cells is essential for memory Th cell generation. In fact, <italic>Cd30</italic>-deficiency resulted in the impaired generation of memory Th1 and Th17 cells, which can be rescued by overexpression of TG2. Furthermore, <italic>transglutaminase-2</italic> (<italic>Tgm2</italic>)-deficient CD4 T cells failed to become memory Th cells. As a result, T cells from <italic>Tgm2</italic>-deficient mice displayed impaired antigen-specific antibody production and attenuated Th17-mediated allergic responses. Our data indicate that CD30-induced TG2 expression in effector Th cells is essential for the generation of memory Th1 and Th17 cells, and that CD30 can be a marker for precursors of memory Th1 and Th17 cells.</p>