IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis.
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-γ. 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.
['Engelbertsen|Daniel|D|', 'Rattik|Sara|S|', 'Wigren|Maria|M|', 'Vallejo|Jenifer|J|', 'Marinkovic|Goran|G|', 'Schiopu|Alexandru|A|', 'Björkbacka|Harry|H|', 'Nilsson|Jan|J|', 'Bengtsson|Eva|E|']
D019264:Adoptive Transfer D000818:Animals D001011:Aorta D001018:Aortic Diseases D050197:Atherosclerosis D002478:Cells, Cultured D003094:Collagen D004195:Disease Models, Animal D018398:Homeodomain Proteins D006801:Humans D007371:Interferon-gamma D020381:Interleukin-17 D008810:Mice, Inbred C57BL D000074085:Mice, Knockout, ApoE D053594:Myeloid Differentiation Factor 88 D010641:Phenotype D058226:Plaque, Atherosclerotic D053573:Receptors, Interleukin-1 Type I D015398:Signal Transduction D058504:Th17 Cells
MyD88 T cells Th17 Atherosclerosis IL-1