Reciprocal modulation of helper Th1 and Th17 cells by the β2‐adrenergic receptor agonist drug terbutaline. (8th August 2017)

• Record Type: Journal Article
• Authors: Carvajal Gonczi, Catalina M.; Tabatabaei Shafiei, Mahdieh; East, Ashley; Martire, Erika; Maurice‐Ventouris, Meagane H.I.; Darlington, Peter J.
• Is Part Of: FEBS journal. Volume 284:Number 18(2017)
• Page Start: 3018
• Page End: 3028
• Publication Date: 2017-08-08
• Subjects: beta 2 adrenergic receptor -- IL‐17A -- norepinephrine -- T helper cells -- terbutaline; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.14166
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Catecholamine hormones are powerful regulators of the immune system produced by the sympathetic nervous system (SNS). They regulate the adaptive immune system by altering T‐cell differentiation into T helper (Th) 1 and Th2 cell subsets, but the effect on Th17 cells is not known. Th17 cells, defined, in part, by chemokine receptor CCR6 and cytokine interleukin (IL)‐17A, are crucial for mediating certain pathogen‐specific responses and are linked with several autoimmune diseases. We demonstrated that a proportion of human Th17 cells express beta 2‐adrenergic receptor (β2AR), a G protein‐coupled receptor that responds to catecholamines. Activation of peripheral blood mononuclear cells, which were obtained from venous blood drawn from healthy volunteers, with anti‐cluster of differentiation 3 (CD3) and anti‐CD28 and with a β2‐agonist drug, terbutaline (TERB), augmented IL‐17A levels ( P < 0.01) in the majority of samples. TERB reduced interferon gamma (IFNγ) indicating that IL‐17A and IFNγ are reciprocally regulated. Similar reciprocal regulation was observed with dbcAMP. Proliferation of Th cells was monitored by carboxyfluorescein diacetate N ‐succinimidyl ester labeling and flow cytometry with antibody staining for CD3 and CD4. TERB increased proliferation by a small but significant margin ( P < 0.001). Next, Th17 cells (CD4 + CXCR3 − CCR6 + ) were purified using an immunomagnetic positive selection kit, which removes all other mononuclear cells. TERB increased IL‐17A from purified Th17 cells, which argues that TERB acts directly on Th17 cells. Thus, hormone signals from the SNS maintain a balance of Th cells subtypes through the β2AR. Abstract : Th17 cells target specific pathogens, but they are also linked with autoimmune diseases. Catecholamine hormones released by the sympathetic nervous system can respond to adrenergic receptors (β2AR). We demonstrated the presence of β2AR on Th17 cells. Terbutaline, a β2‐agonist drug, augmented interleukin‐17A. The drug reduced IFNγ levels indicating that a reciprocal regulation between Th17 and Th1 cells occurred.