Differential IL-10R1 expression plays a critical role in IL-10-mediated immune regulation.

TitleDifferential IL-10R1 expression plays a critical role in IL-10-mediated immune regulation.
Publication TypeJournal Article
Year of Publication2001
AuthorsDing Y, Qin L, Zamarin D, Kotenko SV, Pestka S, Moore KW, Bromberg JS
JournalJ Immunol
Date Published2001 Dec 15
KeywordsAnimals, B-Lymphocytes, Cell Line, Cells, Cultured, CHO Cells, Cricetinae, DNA-Binding Proteins, Humans, Interleukin-10, Lymphocyte Activation, Mast Cells, Mice, Milk Proteins, Protein Isoforms, Receptors, Interleukin, Receptors, Interleukin-10, RNA, Messenger, Signal Transduction, STAT1 Transcription Factor, STAT3 Transcription Factor, STAT5 Transcription Factor, T-Lymphocytes, Trans-Activators, Transcription, Genetic, Viral Proteins

In this study, we characterized the differential receptor-binding specificity, affinity, and Janus kinase-STAT activation of cellular IL-10 (cIL-10) compared with viral IL-10 (vIL-10). Only cells expressing IL-10R1 bind human IL-10 or vIL-10. IL-10R2 does not bind to cIL-10 or vIL-10 alone and its presence does not enhance the receptor-binding affinity of cIL-10 or vIL-10, but it is essential for both cIL-10- and vIL-10-mediated signal transduction and immune regulation. Responses initiated by cIL-10 and vIL-10 were compared in B cell and mast cell lines, and demonstrated that the inability of vIL-10 to stimulate immune responses, as compared with human IL-10, is due to failure to initiate signaling. Absent signal transduction is due to low level expression of cell surface IL-10R1, since overexpressing IL-10R1 allows vIL-10 to initiate cIL-10-like signals and subsequent biological responses. These results are similar in primary cells, since splenocytes respond to both cIL-10 and vIL-10, while thymocytes respond only to cIL-10 and have very low mouse IL-10R1 but not mouse IL-10R2 expression. These data demonstrate that IL-10R1 expression plays a critical role in determining whether cells respond to IL-10. Modulation of cell surface IL-10R1 density might be an important mechanism for determining whether IL-10 leads to immunostimulation or immunosuppression in vivo.

Alternate JournalJ Immunol
PubMed ID11739506
Grant ListR01-CA46465 / CA / NCI NIH HHS / United States
R01 AI44929 / AI / NIAID NIH HHS / United States
R01 AI43369 / AI / NIAID NIH HHS / United States
R01 AI36450 / AI / NIAID NIH HHS / United States
1P30-CA72720 / CA / NCI NIH HHS / United States
Related Faculty: 
Lihui Qin, M.D., Ph.D.

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