IL-4-mediated development of TGF-beta1-producing cells from naïve CD4(+) T cells through a STAT6-independent mechanism.
Transforming growth factor-beta1 (TGF-beta1) is an inhibitory cytokine increasingly recognized as a key factor for immuno-regulation. The function of IL-4 in the regulation of TGF-beta1 production from T cells has been reported previously; however, the precise molecular mechanism still remains to be elucidated. For a better understanding of the mechanism involved in regulation, we have investigated a relationship between the STAT6-dependent pathway and TGF-beta1 production from naïve T cells. TCR crosslinking initiates TGF-beta1 production in CD4(+) T cells, and IL-4-mediated signaling enhances the TGF-beta1 production from naïve CD4(+) T cells. The IL-4-mediated up-regulation of TGF-beta1 production from naïve CD4(+) T cells is elicited in STAT6-deficient (STAT6 KO) mice, but not in IL-4 receptor-deficient (IL-4R KO) mice. These results clearly demonstrate that a STAT6-independent pathway is working in IL-4-mediated enhancement of TGF-beta1 production from naïve CD4(+) T cells. Moreover, the addition of IL-4 showed no additive effect on TGF-beta1 promoter-mediated transcription stimulated by TCR. Therefore, we hypothesize that the IL-4-mediated signaling does not work directly on the transcription of the TGF-beta1 gene, but rather regulates the expansion of TGF-beta1-secreting T cells.
Kohyama
M
M
Research Institute for Biological Sciences, Science University of Tokyo, Chiba, Japan.
Sugahara
D
D
Hosokawa
H
H
Kubo
M
M
Hozumi
N
N
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D019948:Receptors, Interleukin-4 / Q000502:physiology; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma