Interleukin-1β-induced IRAK1 ubiquitination is required for TH-GM-CSF cell differentiation in T cell-mediated inflammation

Yuan Hu, Feihong Xu, Ruihua Zhang, Diana Legarda, Jun Dai, Di Wang, Heyu Li, Yao Zhang, Qingjie Xue, Guanjun Dong, Hui Zhang, Chang Lu, Arthur Mortha, Jianguo Liu, Paolo Cravedi, Adrian Ting, Liwu Li, Chen feng Qi, Susan Pierce, Miriam MeradPeter Heeger, Huabao Xiong

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Accumulating evidence suggests granulocyte macrophage-colony stimulating factor (GM-CSF) can function as an inflammatory mediator, but whether GM-CSF-producing CD4+ T cells (TH-GM-CSF) are a distinct T helper cell subset is lacking. Herein we demonstrate that interleukin (IL)-1β exclusively drives differentiation of naïve CD4+ T cells into TH-GM-CSF cells via inducing ubiquitination of IL-1 receptor-associated kinase 1 (IRAK1) and subsequent activation of the transcription factor NF-kappaB (NF-κB), independent of RAR-related orphan receptor gamma (RORγt) required for TH17 differentiation. In vivo, TH-GM-CSF cells are present in murine Citrobacter Rodentium infections and mediate colitis following adoptive transfer of CD4+ T cells into Rag1−/− mice via GM-CSF-induced macrophage activation. The TH-GM-CSF cell phenotype is stable and distinct from the TH17 genetic program, but IL-1β can convert pre-formed TH17 cells into TH-GM-CSF cells, thereby accounting for previously reported associations between IL-17 and GM-CSF. Together, our results newly identify IL-1β/NF-κB-dependent TH-GM-CSF cells as a unique T helper cell subset and highlight the importance of CD4+ T cell-derived GM-CSF induced macrophage activation as a previously undescribed T cell effector mechanism.

Original languageEnglish (US)
Pages (from-to)50-64
Number of pages15
JournalJournal of Autoimmunity
StatePublished - Aug 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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