| First Author | Engelbertsen D | Year | 2018 |
| Journal | Cardiovasc Res | Volume | 114 |
| Issue | 1 | Pages | 180-187 |
| PubMed ID | 29036304 | Mgi Jnum | J:269285 |
| Mgi Id | MGI:6272228 | Doi | 10.1093/cvr/cvx196 |
| Citation | Engelbertsen D, et al. (2018) IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis. Cardiovasc Res 114(1):180-187 |
| abstractText | Aims: The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. Methods and results: We transferred apoe-/-myd88+/+ or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88+/+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-gamma. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells. Conclusion: We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels. |
