TY - JOUR
T1 - Regulating human Th17 cells via differential expression of IL-1 receptor
AU - Lee, Won Woo
AU - Kang, Seong Wook
AU - Choi, Jihoon
AU - Lee, Seung Hyun
AU - Shah, Kamini
AU - Eynon, Elizabeth E.
AU - Flavell, Richard A.
AU - Kang, Insoo
PY - 2010/1/21
Y1 - 2010/1/21
N2 - In humans, interleukin-1β (IL-1β) has been suggested as an essential cytokine for developing IL-17- or IL-17A-producing CD4+ T helper 17 (Th17) cells. However, little is known about the relationship of IL-1 receptor expression and Th17 cell differentiation. We report here the presence of 2 distinct CD4+ T-cell populations with and without expression of IL-1RI that correlates with the capacity to produce IL-17 in naive and memory CD4+ T cells of human peripheral blood. IL-1RI+ memory CD4+ T cells had increased gene expression of IL17, RORC, and IRF4 even before T-cell receptor triggering, indicating that the effect of IL-1β is programmed in these cells via IL-1RI. Although CD4+ T cells from umbilical cord blood did not express IL-1RI, the cytokines IL-7, IL-15, and transforming growth factor-β (TGF-β) up-regulated IL-1RI expression on naive CD4+ T cells, suggesting that IL-1RI+ naive CD4+ T cells develop in periphery. Furthermore, IL-17 production from the cytokine-treated naiveCD4+ T cells was induced by IL-1β and this induction was blocked by IL-1R antagonist. These results indicate that human Th17 cell differentiation is regulated via differential expression of IL-1RI, which is controlled by IL-7 and IL-15.
AB - In humans, interleukin-1β (IL-1β) has been suggested as an essential cytokine for developing IL-17- or IL-17A-producing CD4+ T helper 17 (Th17) cells. However, little is known about the relationship of IL-1 receptor expression and Th17 cell differentiation. We report here the presence of 2 distinct CD4+ T-cell populations with and without expression of IL-1RI that correlates with the capacity to produce IL-17 in naive and memory CD4+ T cells of human peripheral blood. IL-1RI+ memory CD4+ T cells had increased gene expression of IL17, RORC, and IRF4 even before T-cell receptor triggering, indicating that the effect of IL-1β is programmed in these cells via IL-1RI. Although CD4+ T cells from umbilical cord blood did not express IL-1RI, the cytokines IL-7, IL-15, and transforming growth factor-β (TGF-β) up-regulated IL-1RI expression on naive CD4+ T cells, suggesting that IL-1RI+ naive CD4+ T cells develop in periphery. Furthermore, IL-17 production from the cytokine-treated naiveCD4+ T cells was induced by IL-1β and this induction was blocked by IL-1R antagonist. These results indicate that human Th17 cell differentiation is regulated via differential expression of IL-1RI, which is controlled by IL-7 and IL-15.
UR - http://www.scopus.com/inward/record.url?scp=77449112013&partnerID=8YFLogxK
U2 - 10.1182/blood-2009-08-236521
DO - 10.1182/blood-2009-08-236521
M3 - Article
C2 - 19965648
AN - SCOPUS:77449112013
SN - 0006-4971
VL - 115
SP - 530
EP - 540
JO - Blood
JF - Blood
IS - 3
ER -