Interleukin-4 supports the suppressive immune responses elicited by regulatory T cells

Wei Cheng Yang, Yih Shiou Hwang, Ying Yu Chen, Chao Lin Liu, Chia Ning Shen, Wei Hsin Hong, Sheng Min Lo, Chia Rui Shen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

54 Scopus citations


Interleukin-4 (IL-4) has been considered as one of the tolerogenic cytokines in many autoimmune animal models and clinical settings. Despite its role in antagonizing pathogenic Th1 responses, little is known about whether IL-4 possesses functions that affect regulatory T cells (Tregs). Tregs are specialized cells responsible for the maintenance of peripheral tolerance through their immune modulatory capabilities. Interestingly, it has been suggested that IL-4 supplement at a high concentration protects responder T cells (Tresps) from Treg-mediated immune suppression. In addition, such supplement also impedes TGF-β-induced Treg differentiation in vitro. However, these phenomena may contradict the tolerogenic role of IL-4, and the effects of IL-4 on Tregs are therefore needed to be further elucidated. In this study, we utilized IL-4 knockout (KO) mice to validate the role of IL-4 on Treg-mediated immune suppression. Although IL-4 KO and control animals harbor similar frequencies of Tregs, Tregs from IL-4 KO mice weakly suppressed autologous Tresp activation. In addition, IL-4 deprivation impaired the ability of Tregs to modulate immune response, whereas IL-4 supplementation reinforced IL-4 KO Tregs in their function in suppressing Tresps. Finally, the presence of IL-4 was associated with increased cell survival and granzyme expression of Tregs. These results suggest the essential role of IL-4 in supporting Treg-mediated immune suppression, which may benefit the development of therapeutic strategies for autoimmune diseases.

Original languageEnglish
Article number1508
JournalFrontiers in Immunology
Issue numberNOV
StatePublished - 14 11 2017

Bibliographical note

Publisher Copyright:
© 2017 Yang, Hwang, Chen, Liu, Shen, Hong, Lo and Shen.


  • Cell survival
  • Granzyme
  • Immunosuppression
  • Interleukin-4
  • Regulatory T cell


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