Promotion of regulatory B cell function by catecholamines - implications for autoimmune arthritis

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Main goal of the project is a better understanding of the modulation of regulatory B cells by catecholamines to derive new treatment targets for autoimmunity, with a focus on autoimmune arthritis. It is known that catecholamines, wich are provided in the microenvironment by the sympathetic nervous system or catecholamine producing, tyrosin hydroxylase (TH) positive cells, are modulators of autoimmune diseases. Adrenergic receptors, especially beta-2 adrenoceptors, which are expressed on almost all immune cells, directly mediate this regulation. We could show in recent work in a model of rheumatoid arthritis (collagen-induced arthritis in mice) that catecholamines via acting on regulatory B cells (increase in IL-10) show anti-inflammatory properties and improve arthritis. In the proposed project we want to investigate, which catecholaime-dependent mechanisms lead to an increase in regulatory B cell function, if these mechanisms can be targeted to influence regulatory B cell function, if these mechanisms are also established in the human system, and if they are pathophysiologically relevant. If we succeed in better understanding and manipulating these mechanisms this would provide us with a means to develop novel treatment strategies, especially for rheumatoid arthritis, along with a better understanding of regulatory B cell physiology. However, results from this project might play a broader role for inflammatory diseases, where regulatory B cells are involved in pathophysiology.