title: Interleukin-21 induces the differentiation of human Tc22 cells via phosphorylation of signal transducers and activators of transcription.
abstract: Interleukin-21 (IL-21) exerts critical functions in T helper type 17 (Th17) cell development. However, the effect of IL-21 on the differentiation of IL-22-producing T cells is not clear. Here we showed that IL-21 induced the differentiation of human naive CD8(+) T cells into Tc22 cells without the expression of IL-17. The addition of transforming growth factor-β inhibited the production of IL-22 but induced the production of IL-17. Both IL-15 and IL-2 induced interferon-γ production but did not induce differentiation of Tc22, which suggests that common γ-chain signals are not specific to promote IL-22 synthesis. The IL-21 induced naive CD8(+) T cells to produce IL-22 in greater amounts than memory CD8(+) T cells. In addition, we demonstrated that IL-21 promoted the proliferation and increased the expression of IL-21 receptors on activated naive CD8(+) T cells. Furthermore, IL-21 increased the expression of granzyme B molecules. Analysis of molecular mechanisms indicated that IL-21 induced phosphorylation of signal transducers and activators of transcription 1, 3 and 5 in CD8(+) T cells. Overall, our data indicated that IL-21, an effector cytokine produced by CD4(+) T cells, might mediate the cross-talk between CD4(+) and CD8(+) T cells through the production of IL-22.
authors.affiliation: Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Binyan
authors.initials: B
authors.lastname: Yang
authors.forename: Jiangjun
authors.initials: J
authors.lastname: Ma
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Fengyu
authors.initials: F
authors.lastname: Huang
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Changyou
authors.initials: C
authors.lastname: Wu
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D005434:Flow Cytometry; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D053655:Receptors, Interleukin-21 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D055815:Young Adult; D000097043:Interleukin-22; D000098546:Interleukin-21
chemical_list: D053804:Granzymes; D007378:Interleukins; D053655:Receptors, Interleukin-21; D050791:STAT Transcription Factors; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D000097043:Interleukin-22; D000098546:Interleukin-21