Beta-adrenergic receptors ADRB1 and ADRB2 regulate formation of memory CD8 T cells 2260268

Abstract

Abstract Introduction Memory CD8 T cells persist long term in tissues and protect the body against reinfection over multiple decades. Both lymphoid and non-lymphoid tissues are innervated by sympathetic nerves, which mediate the body’s response to stress and release the stress hormone noradrenaline. However, it is not understood how the sympathetic nerves in peripheral tissues control the function of immune cells and their response to acute viral infections. Methods To address this, we used genetic knockout mice to disrupt the expression of the noradrenaline receptors ADRB1 and ADRB2 on antigen-specific CD8 T cells during acute LCMV Armstrong infection. Results Our data show that loss of Adrb1 promotes the formation of memory precursor and central memory T cells, while loss of Adrb2 promotes terminal differentiation of CD8 T cells. RNA-seq analysis revealed that Adrb1-deficiency promotes memory gene expression programming. Expression of both Adrb1 and Adrb2 are regulated by type 1 interferons. Conclusion Given that Adrb1 and Adrb2 influence T cell differentiation in distinct and opposing manners, we hypothesize there is differential signaling downstream of the receptors, which we are currently investigating. These studies will yield insights into the mechanisms of communication between the nervous and immune systems and how they impact the immune response to acute viral infection. Funding Source n/a Topic Categories Neuroimmunology (NEUR)