Mouse T Cells Express a Neurotransmitter-receptor Signature That is Quantitatively Modulated in a Subset- and Activation-dependent Manner

Neurotransmitters are known to modulate the course of an immune response by targeting cells in both the innate and adaptive immune systems. Increasing evidence suggests that T cells, by expressing specific neurotransmitter receptors (NR) are directly regulated by them, leading to altered activation and skewed differentiation of the adaptive immune response. Given that gene expression in T cells changes in lineage- and activation-dependent fashion, it is expected that sensitivity to neurotransmitters may also vary along these lines. Here we generate an important resource for further analysis of this tier of immunoregulation, by identifying the distinct profile of NR transcripts that are expressed by peripheral T cells in mice, at different states of activation and differentiation. We find that only about 15% of the total annotated NR genes are transcribed in these T cells and most of them do not change in different subsets of T cells (CD8, CD4 - Naïve vs Memory vs Treg), or even when T cells migrate to different tissues. We suggest that the T cell-expressed NRs, found across all these subsets identifies a core, constitutive NR signature for the T cell lineage. In contrast, a very limited number (<2) of NRs were observed to mark each of the post-activation T cell states, suggesting that very specific neurotransmitter signals are available to modulate T cell responses in vivo in these subsets.