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Reciprocal modulation of helper Th1 and Th17 cells by the β2‐adrenergic receptor agonist drug terbutaline
Author(s) -
Carvajal Gonczi Catalina M.,
Tabatabaei Shafiei Mahdieh,
East Ashley,
Martire Erika,
MauriceVentouris Meagane H.I.,
Darlington Peter J.
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14166
Subject(s) - c c chemokine receptor type 6 , biology , immune system , endocrinology , microbiology and biotechnology , cytokine , medicine , chemistry , immunology , chemokine , chemokine receptor
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 CCR 6 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‐ CD 28 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 IFN γ are reciprocally regulated. Similar reciprocal regulation was observed with dbc AMP . Proliferation of Th cells was monitored by carboxyfluorescein diacetate N ‐succinimidyl ester labeling and flow cytometry with antibody staining for CD 3 and CD 4. TERB increased proliferation by a small but significant margin ( P < 0.001). Next, Th17 cells ( CD 4 + CXCR 3 − CCR 6 + ) 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.