Deletion of muscarinic type 1 acetylcholine receptors alters splenic lymphocyte functions and splenic noradrenaline concentration

•Splenic noradrenaline concentration is increased in muscarinic type 1 acetylcholine receptor knockout (M1KO) mice.•This parameter is unaltered in mice heterozygous for acetylcholinesterase (AChE +/−).•M1KO mice have decreased numbers of IgG secreting cells in the spleen.•M1KO cells display increased CD4+ T cell-dependent in vitro-induced cytotoxicity.•In vitro CD4+ T cell proliferation is increased in AChE +/− mice.

The existence of interactions between the immune and the sympathetic nervous systems is well established. Noradrenaline can promote or inhibit the immune response, and conversely, the immune response itself can affect noradrenaline concentration in lymphoid organs, such as the spleen. It is also well known that acetylcholine released by pre-ganglionic neurons can modulate noradrenaline release by the postsynaptic neuron. The spleen does not receive cholinergic innervation, but it has been reported that lymphocytes themselves can produce acetylcholine, and express acetylcholine receptors and acetylcholinesterase. We found that the spleen of not overtly immunized mice in which muscarinic type 1 acetylcholine receptors have been knocked out (M1KO) has higher noradrenaline concentrations than that of the wildtype mice, without comparable alterations in the heart, in parallel to a decreased number of IgG-producing B cells. Splenic lymphocytes from M1KO mice displayed increased in vitro-induced cytotoxicity, and this was observed only when CD4+ T cells were present. In contrast, heterozygous acetylcholinesterase (AChE +/−) mice, had no alterations in splenic noradrenaline concentration, but the in vitro proliferation of AChE +/− CD4+ T cells was increased. It is theoretically conceivable that reciprocal effects between neuronally and non-neuronally derived acetylcholine and noradrenaline might contribute to the results reported. Our results emphasize the need to consider the balance between the effects of these mediators for the final immunoregulatory outcome.