T cell-intrinsic IL-1R signaling licenses effector cytokine production by memory CD4 T cells

Nat Commun. 2018 Aug 9;9(1):3185. doi: 10.1038/s41467-018-05489-7.


Innate cytokines are critical drivers of priming and differentiation of naive CD4 T cells, but their functions in memory T cell response are largely undefined. Here we show that IL-1 acts as a licensing signal to permit effector cytokine production by pre-committed Th1 (IFN-γ), Th2 (IL-13, IL-4, and IL-5) and Th17 (IL-17A, IL-17F, and IL-22) lineage cells. This licensing function of IL-1 is conserved across effector CD4 T cells generated by diverse immunological insults. IL-1R signaling stabilizes cytokine transcripts to enable productive and rapid effector functions. We also demonstrate that successful lineage commitment does not translate into productive effector functions in the absence of IL-1R signaling. Acute abrogation of IL-1R signaling in vivo results in reduced IL-17A production by intestinal Th17 cells. These results extend the role of innate cytokines beyond CD4 T cell priming and establish IL-1 as a licensing signal for memory CD4 T cell function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • Cell Lineage
  • Cell Proliferation
  • Cytokines / metabolism*
  • Dendritic Cells / metabolism
  • Humans
  • Hyaluronan Receptors / metabolism
  • Immunologic Memory*
  • Interleukin-17 / metabolism
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • L-Selectin / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloid Differentiation Factor 88 / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-1 Type I / genetics
  • Receptors, Interleukin-1 Type I / metabolism*
  • Signal Transduction
  • Spleen / metabolism


  • CD44 protein, human
  • Cd44 protein, mouse
  • Cytokines
  • Hyaluronan Receptors
  • IL17A protein, human
  • IL1R1 protein, human
  • IL1R1 protein, mouse
  • Il17a protein, mouse
  • Interleukin-17
  • Interleukin-18
  • Interleukin-1beta
  • MYD88 protein, human
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • RNA, Messenger
  • Receptors, Interleukin-1 Type I
  • L-Selectin