Regulating human Th17 cells via differential expression of IL-1 receptor.
In humans, interleukin-1beta (IL-1beta) 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-1beta 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-beta (TGF-beta) 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 naive CD4(+) T cells was induced by IL-1beta 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.
Lee
Won-Woo
WW
Department of Internal Medicine Yale University School of Medicine, New Haven, CT, USA.
Kang
Seong Wook
SW
Choi
Jihoon
J
Lee
Seung-Hyun
SH
Shah
Kamini
K
Eynon
Elizabeth E
EE
Flavell
Richard A
RA
Kang
Insoo
I
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D019409:Interleukin-15 / Q000494:pharmacology / Q000502:physiology; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D017472:Receptors, Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D019409:Interleukin-15; D020381:Interleukin-17; D053583:Interleukin-1beta; D015851:Interleukin-7; D017472:Receptors, Interleukin-1; D016212:Transforming Growth Factor beta