Sustained Alleviation of Autoimmunity by Activating α2B-adrenergic Receptors.
J Immunol
; 213(4): 435-441, 2024 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-38940628
ABSTRACT
Catecholamines binding to α- and ß-adrenergic receptors on immune cells have recently been shown to play an important role in regulating immune responses. Although α2-adrenergic receptors are known to modulate the immune response in different ways, the therapeutic exploration of their utility has been limited by the lack of agonists selective for the three α2-adrenergic subtypes. We report in this study the identification of the agonist AGN-762, which activates α2B- and α2C-adrenergic subtypes, but not the α2A subtype. We show that AGN-762 reduced clinical disease in an experimental autoimmune encephalitis model of autoimmune disease via direct or indirect effects on T regulatory cells. The activity of AGN-762 was abrogated by depletion of T regulatory cells, which express the α2B-adrenergic receptor. Furthermore, a drug-induced shift to an anti-inflammatory phenotype was demonstrated in immune cells in the spleen of drug-treated experimental autoimmune encephalitis mice. AGN-762 does not display sedative and cardiovascular side effects associated with α2A subtype agonists. Immune modulation by selective α2-adrenergic agonists represents a novel, to our knowledge, approach for treating autoimmune disease.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Autoinmunidad
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Receptores Adrenérgicos alfa 2
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Agonistas de Receptores Adrenérgicos alfa 2
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Immunol
Año:
2024
Tipo del documento:
Article