Noradrenaline through β-adrenoceptor contributes to sexual dimorphism in primary CD4+ T-cell response in DA rat EAE model?

•Noradrenaline level/cell content is greater in male than female EAE rat dLNs.•β2-AR+ cell frequency is higher in male than female EAE rat dLN CD4+ and CD11b+ cells.•Propranolol (P) increases IL-2 level and CD4+ cell proliferation in dLN cell cultures.•P augments Th17 cell differentiation and IL-17 level in dLN cell cultures.•P augments IL-17 production only in Th17 cells from male rat dLN cell cultures. Males exhibit stronger sympathetic nervous system (SNS) activity, but weaker primary CD4+ T-cell (auto)immune responses. To test the role of catecholamines, major end-point SNS mediators, in this dimorphism, influence of propranolol (β-adrenoceptor blocker) on mitogen/neuroantigen-stimulated CD4+ T cells from female and male EAE rat draining lymph node (dLN) cell cultures was examined. Male rat dLNs exhibited higher noradrenaline concentration and frequency of β2-adrenoceptor–expressing CD4+ T lymphocytes and antigen presenting cells. Propranolol, irrespective of exogenous noradrenaline presence, more prominently augmented IL-2 production and proliferation of CD4+ lymphocytes in male than female rat dLN cell cultures. In neuroantigen-stimulated dLN cells of both sexes propranolol increased IL-1β and IL-23/p19 expression and IL-17+ CD4+ cell frequency, but enhanced IL-17 production only in male rat CD4+ lymphocytes, thereby abrogating sexual dimorphism in IL-17 concentration observed in propranolol-free cultures. Thus, β-adrenoceptor–mediated signalling may contribute to sex bias in rat IL-17–producing cell secretory capacity.