TY - JOUR
T1 - T cell-intrinsic IL-1R signaling licenses effector cytokine production by memory CD4 T cells
AU - Jain, Aakanksha
AU - Song, Ran
AU - Wakeland, Edward K.
AU - Pasare, Chandrashekhar
N1 - Funding Information:
We thank all members of the Pasare lab for helpful discussions. Thanks yo Rustam Bagirzadeh for critical reading of the manuscript. Yajing Gao and Garrett Overcast helped with cell isolations. Fayyaz S. Sutterwala, M.D., Ph.D. at Cedars-Sinai, LA, generously provided Il1α−/− and Il1β−/− mice. This work was supported by grants from the National Institutes of Health (AI113125 and AI123176) to C.P.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-05489-7
DO - 10.1038/s41467-018-05489-7
M3 - Article
C2 - 30093707
AN - SCOPUS:85051301079
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3185
ER -