| First Author | Abdi K | Year | 2022 |
| Journal | Eur J Immunol | Volume | 52 |
| Issue | 9 | Pages | 1431-1440 |
| PubMed ID | 35816444 | Mgi Jnum | J:330803 |
| Mgi Id | MGI:7330286 | Doi | 10.1002/eji.202149733 |
| Citation | Abdi K, et al. (2022) Dendritic cells Trigger IFN-gamma secretion by NK cells independent of IL-12 and IL-18. Eur J Immunol |
| abstractText | It is commonly believed that IL-12 produced by DCs in response to pathogens is the first signal that stimulates the production of IFN-gamma by NK cells. However, IL-12 production by DCs in response to bacterial LPS depends on either engagement of CD40 by CD40L on activated T cells or IFN-gamma from NK cells. This suggests that during the primary immune response, NK cells produce IFN-gamma before IL-12 production by DCs. Here, using single-cell measurements, cell sorting and mouse lines deficient in IL-12, IL-23, type I IFN receptor and the IL-18 receptor, we show that a subset of BM-derived DCs characterized by low expression of MHC class II (MHCII(low) ) stimulates IFN-gamma production by NK cells. The expression of Toll-like Receptor (TLR) 4 on DCs but not NK cells was required for such NK-derived IFN-gamma. In addition, soluble factor(s) produced by LPS-activated MHCII(low) DCs were sufficient to induce IFN-gamma production by NK cells independent of IL-12, IL-23, and IL-18. This response was enhanced in the presence of a low dose of IL-2. These results delineate a previously unknown pathway of DC-mediated IFN-gamma production by NK cells, which is independent of commonly known cytokines. |
