Multiparametric analysis of cytokine-driven human Th17 differentiation reveals a differential regulation of IL-17 and IL-22 production.
T helper 17 (Th17) cells produce IL-17 but can also make tumor necrosis factor, interleukin (IL)-6, IL-10, IL-21, and IL-22. These cytokines collectively contribute to the functional outcome of the Th response. IL-22 plays a critical role in some Th17-associated diseases, such as psoriasis, but its relationship to IL-17 remains controversial. Here, we used a systematic multiparametric analysis of Th-17-associated cytokines, which revealed the unexpected finding that the regulation pattern of IL-22 was most closely related to interferon-gamma, the prototypical Th1 cytokine, and not to IL-17. To explain this observation, we systematically tested the role of Th1- and Th17-inducing cytokines. We could show that IL-12 and IL-23 induced high levels of IL-22 but no IL-17. Conversely, transforming growth factor-beta inhibited IL-22 production but promoted IL-17. Thus, IL-17 and IL-22 are differentially regulated during cytokine-induced Th cell differentiation. This has important implications for the understanding and pharmacologic manipulation of Th17-associated pathologies.
Volpe
Elisabetta
E
Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France.
Touzot
Maxime
M
Servant
Nicolas
N
Marloie-Provost
Marie-Annick
MA
Hupé
Philippe
P
Barillot
Emmanuel
E
Soumelis
Vassili
V
D015153:Blotting, Western; D002454:Cell Differentiation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000097043:Interleukin-22
D007371:Interferon-gamma; D020381:Interleukin-17; D007378:Interleukins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000097043:Interleukin-22