Thioperamide induces CD4⁺ CD25⁺ Foxp3⁺ regulatory T lymphocytes in the lung mucosa of allergic mice through its action on dendritic cells

Maria Marta Amaral^1*, Carolina A Alvarez^1*, Cecilia Langellotti², Carolina Jancic¹, Gabriela Salamone¹, Jorge Geffner¹, Mónica Vermeulen¹,
¹Institute of Hematologic Research, National Academy of Medicine, Buenos Aires, Argentina; ²Institute of Virology, CICVyA, INTA, Castelar, Argentina
^*Authors contributed equally to this work

Background: Histamine is an important mediator in the development of allergic reactions. The biological effects of histamine are mediated through four histaminergic receptors. In recent years, an important role has been assigned to the proinflammatory functions of histamine regarding the H4 receptor. Previously, we have demonstrated that injection of immature dendritic cells treated with histamine into allergic mice promotes an increase in CD8⁺ Tc2 lymphocytes, which are involved in the worsening of allergy symptoms during the chronic phase of the disease. The aim of this study was to evaluate the role of the H3/H4 receptor antagonist, thioperamide, in allergy.
Methods: Ovalbumin-allergized mice and nonallergized mice were injected with phosphate-buffered saline, dendritic cells, or thioperamide-treated dendritic cells. After treatment, the lungs of the mice were obtained and analyzed for changes in the populations of dendritic cells and T lymphocytes, as well as the expression of H and H4 receptors in mononuclear lung cells.
Results: We found an increase in regulatory T cells in the lungs of allergic mice intratracheally injected with dendritic cells which had their H3/H4 receptors blocked with thioperamide. We also found an increase in the production of interleukin-10 by dendritic cells of the lung. Finally, we observed a decrease in serum levels of specific anti-IgE and a reduction of eosinophils in bronchoalveolar lavage from allergic mice.
Conclusion: Thioperamide induces a significant improvement in symptoms of allergic reaction perhaps via induction of regulatory T lymphocytes. These findings may become relevant in the understanding of type 1 hypersensivity reactions.

Keywords: dendritic cells, regulatory T lymphocytes, thioperamide, histamine, allergy