| First Author | Vigne S | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 22 | Pages | 5813-23 |
| PubMed ID | 21860022 | Mgi Jnum | J:178804 |
| Mgi Id | MGI:5300146 | Doi | 10.1182/blood-2011-05-356873 |
| Citation | Vigne S, et al. (2011) IL-36R ligands are potent regulators of dendritic and T cells. Blood 118(22):5813-23 |
| abstractText | IL-36alpha (IL-1F6), IL-36beta (IL-1F8), and IL-36gamma (IL-1F9) are members of the IL-1 family of cytokines. These cytokines bind to IL-36R (IL-1Rrp2) and IL-1RAcP, activating similar intracellular signals as IL-1, whereas IL-36Ra (IL-1F5) acts as an IL-36R antagonist (IL-36Ra). In this study, we show that both murine bone marrow-derived dendritic cells (BMDCs) and CD4(+) T lymphocytes constitutively express IL-36R and respond to IL-36alpha, IL-36beta, and IL-36gamma. IL-36 induced the production of proinflammatory cytokines, including IL-12, IL-1beta, IL-6, TNF-alpha, and IL-23 by BMDCs with a more potent stimulatory effect than that of other IL-1 cytokines. In addition, IL-36beta enhanced the expression of CD80, CD86, and MHC class II by BMDCs. IL-36 also induced the production of IFN-gamma, IL-4, and IL-17 by CD4(+) T cells and cultured splenocytes. These stimulatory effects were antagonized by IL-36Ra when used in 100- to 1000-fold molar excess. The immunization of mice with IL-36beta significantly and specifically promoted Th1 responses. Our data thus indicate a critical role of IL-36R ligands in the interface between innate and adaptive immunity, leading to the stimulation of T helper responses. |
