Abstract
Disorder of the sympathetic nervous system (SNS) is closely related to the pathogenesis of various autoimmune diseases (ADs). Catecholamine triggered beta2-adrenergic receptor (β2-AR) signaling is important in creating a bidirectional response in the progression of ADs due to factors including diverse expression patterns, single nucleotide polymorphisms (SNPs), biased signals, and desensitization of β2-AR, as well as different subtypes of Gα binding to β2-AR. In this review, we summarize the actions of β2-AR signaling in regulating the functions of immunocytes and in the pathogenesis of ADs, and the application of β2-AR agonists or antagonists in treating major types of ADs is also discussed. We suggest that restoring the immune balance via a soft regulation of the expression or activation of β2-AR is one of the promising therapeutic strategies for systematic ADs.
Highlights
The current understanding of the pathogenesis of autoimmune diseases (ADs) such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), myasthenia gravis (MG), and Grave’s disease (GD) is unsettled; many ADs hold in common the expression of autoantigens, abnormal immunoregulation, and shared genetic factors (Harris et al, 2018)
Β2-AR signaling promotes the expression of IgE and its regulator soluble CD23 through downstream protein kinase A (PKA) and p38 mitogen-activated protein kinase (MAPK) pathways in B cells (Sergienko et al, 2012). These studies portray a picture where a reduction in β2-AR signaling in B cells of individuals with AD is associated with unchecked B cell proliferation, increased autoantibody production, and a reduction in immune response upon challenge
Stimulation of β2-AR on peripheral blood mononuclear cells (PBMCs) inhibits interferon alpha-1 (IFNA1) production mediated by Toll like receptor 9 (TLR9) (Hilbert et al, 2013)
Summary
The current understanding of the pathogenesis of autoimmune diseases (ADs) such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), myasthenia gravis (MG), and Grave’s disease (GD) is unsettled; many ADs hold in common the expression of autoantigens, abnormal immunoregulation, and shared genetic factors (Harris et al, 2018). Autoantibodies produced by B cells are widely observed in the majority of ADs. When activated, β2-AR initially couples with Gαs to promote physiological production of cAMP and inhibit the proliferation of human peripheral B cells (Faisy et al, 2010). Antigen exposed B cells or β2-AR agonist terbutaline treated B cells express higher level of CD86 than resting B cells, combining with CD86 stimulation, IgG1 and IgE production is obvious increased in IL-4 dependent manner. Β2-AR signaling promotes the expression of IgE and its regulator soluble CD23 through downstream PKA and p38 MAPK pathways in B cells (Sergienko et al, 2012) Taken together, these studies portray a picture where a reduction in β2-AR signaling in B cells of individuals with AD is associated with unchecked B cell proliferation, increased autoantibody production, and a reduction in immune response upon challenge. The different mechanisms on B cell activation and isotype switching provide a clinical therapeutic target in IgG1 or IgE responsemediated diseases
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