Runx3 inhibits IL-4 production in T cells via physical interaction with NFAT.
Interleukin (IL)-4 plays a key role in T helper 2 (Th2) cell differentiation favoring humoral immune response. Regulation of IL-4 gene expression, therefore, is critically important for Th2 dependent responses and Th2 dominant disorders. In T cells, IL-4 gene expression is regulated positively or negatively by a combination of several transcription factors. Recently, enhanced IL-4 production was reported in Runx3 knockout mice; this implies negative regulation of IL-4 by Runx3. Runx proteins are transcription factors that have a Runt domain and have essential functions in development. In this study, the molecular mechanism that downregulates IL-4 expression was investigated. Runx3 inhibited IL-4 production in EL-4 T cells stimulated with PMA/ionomycin. Runx3-mediated IL-4 inhibition was NFAT-dependent, and Runx3 was physically associated with NFAT. Therefore, our results suggest that the interaction between NFAT and Runx3 is a mechanism that causes the negative regulation of IL-4, along with previously reported repression by T-bet.
Lee
Sung Ho
SH
College of Pharmacy & Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Jeong
Hyung Min
HM
Choi
Jin Myung
JM
Cho
Young-Chang
YC
Kim
Tae Sung
TS
Lee
Kwang Youl
KY
Kang
Bok Yun
BY