Interleukin-23-induced interleukin-23 receptor subunit expression is mediated by the Janus kinase/signal transducer and activation of transcription pathway in human CD4 T cells.
Interleukin (IL)-23 plays a critical role in the development of the T helper (Th) cell response and is responsible for the maintenance of the IL-17 producing subset of Th cells, Th17. IL-23 is a heterodimeric cytokine composed of IL-23p19 and IL-12p40 subunits, and the signaling pathway for IL-23 involves 2 receptor chains: IL-12Rβ1 and IL-23Rα. The IL-23 receptor complex is expressed on a number of cells, including natural killer cells, monocytes, macrophages, dendritic cells, and CD4 T cells. Currently, the molecular mechanisms governing expression of the IL-23 receptor chains, IL-23Rα and IL-12Rβ1, are not well understood. Our results show that IL-23 induces upregulation of IL-23Rα and IL-12Rβ1 expression in human CD4 T cells. Further, we demonstrate that inhibition of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) pathway by SD-1029, a JAK2 inhibitor, 5'-deoxy-5'-(methylthio) adenosine, a STAT1 inhibitor, and STAT3 VII, a STAT3 inhibitor, were able to block IL-23-induced expression of IL-23 receptor subunits in the human SUPT-1 T cell line and in primary CD4 human T cells. Taken together, our results suggest a positive feedback regulation of the IL-23 receptor via IL-23-mediated activation of the JAK/STAT pathway.
Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada.
Nor Fazila
NF
Che Mat
Xiubo
X
Zhang
Christina
C
Guzzo
Katrina
K
Gee
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D053759:Interleukin-23 / Q000276:immunology*; D053612:Janus Kinases / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics* / Q000276:immunology; D018123:Receptors, Interleukin / Q000235:genetics* / Q000276:immunology; D050791:STAT Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation
C515500:IL23R protein, human; D053759:Interleukin-23; D021122:Protein Subunits; D018123:Receptors, Interleukin; D050791:STAT Transcription Factors; D053612:Janus Kinases