Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides.
Th17 cells are a distinct lineage of effector CD4(+) T cells characterized by their production of interleukin (IL)-17. We demonstrate that Th17 cells also expressed IL-22, an IL-10 family member, at substantially higher amounts than T helper (Th)1 or Th2 cells. Similar to IL-17A, IL-22 expression was initiated by transforming growth factor beta signaling in the context of IL-6 and other proinflammatory cytokines. The subsequent expansion of IL-22-producing cells was dependent on IL-23. We further demonstrate that IL-22 was coexpressed in vitro and in vivo with both IL-17A and IL-17F. To study a functional relationship among these cytokines, we examined the expression of antimicrobial peptides by primary keratinocytes treated with combinations of IL-22, IL-17A, and IL-17F. IL-22 in conjunction with IL-17A or IL-17F synergistically induced the expression of beta-defensin 2 and S100A9 and additively enhanced the expression of S100A7 and S100A8. Collectively, we have identified IL-22 as a new cytokine expressed by Th17 cells that synergizes with IL-17A or IL-17F to regulate genes associated with skin innate immunity.
Liang
Spencer C
SC
Wyeth Research, Cambridge, MA 02140, USA.
Tan
Xiang-Yang
XY
Luxenberg
Deborah P
DP
Karim
Riyez
R
Dunussi-Joannopoulos
Kyriaki
K
Collins
Mary
M
Fouser
Lynette A
LA
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000097043:Interleukin-22
D023181:Antimicrobial Cationic Peptides; D020381:Interleukin-17; D007378:Interleukins; D016212:Transforming Growth Factor beta; D000097043:Interleukin-22