Monocytes differentiated with GM-CSF and IL-15 initiate Th17 and Th1 responses that are contact-dependent and mediated by IL-15

Journal of Leukocyte Biology

Kristina M. Harris¹ 

[1] Pathology Department, University of Maryland School of Medicine, Baltimore, Maryland, USAPathology Department, University of Maryland School of Medicine, Baltimore, Maryland, USAPathology Department, University of Maryland School of Medicine, Baltimore, Maryland, USA

关键词: human immunology;    TLRs;    IL-1β;    IL-23;    inflammation;   

DOI  :  10.1189/jlb.0311132

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Distinct types of DCs are generated from monocytes using GM-CSF with IL-4 (IL4-DC) or IL-15 (IL15-DC). IL15-DCs are potent inducers of antigen-specific CD8+ T cells, display a phenotype similar to CD14+ cells commonly described in chronically inflamed tissues, and produce high levels of IL-1β and IL-15 in response to TLR4 stimulation. As these cytokines promote Th17 responses, which are also associated with inflammatory diseases, I hypothesized that TLR-primed IL15-DCs favor Th17 activation over IL4-DCs. Compared with IL4-DCs, IL15-DCs stimulated with TLR agonists secreted significantly higher concentrations of the Th17-promoting factors, IL-1β, IL-6, IL-23, and CCL20, and lower levels of the Th1 cytokine, IL-12. In addition, IL15-DCs and not IL4-DCs up-regulated IL-15 on the cell surface in response to TLR agonists. IL15-DCs primed with TLR3 or TLR4 agonists triggered Th17 (IL-17, IL-22, and/or IFN-γ) and Th1 (IFN-γ) responses, whereas IL4-DCs primed with the same TLR agonists activated Th1 (IFN-γ) responses. Secretion of IL-17 and IFN-γ required contact with TLR-primed IL15-DC, and IFN-γ production was mediated by membrane-bound IL-15. These findings identify key differences in monocyte-derived DCs, which impact adaptive immunity, and provide primary evidence that IL-15 promotes Th17 and Th1 responses by skewing monocytes into IL15-DC.

【 授权许可】

Unknown