Histamine H4 Receptor Optimizes T Regulatory Cell Frequency and Facilitates Anti-Inflammatory Responses within the Central Nervous System

摘要: Histamine is a biogenic amine that mediates multiple physiological processes, including immunomodulatory effects in allergic and inflammatory reactions, also plays key regulatory role experimental encephalomyelitis, the autoimmune model of sclerosis. The pleiotropic histamine are mediated by four G protein-coupled receptors, as follows: Hrh1/H(1)R, Hrh2/H(2)R, Hrh3/H(3)R, Hrh4/H(4)R. H(4)R expression primarily restricted to hematopoietic cells, its demyelinating disease CNS has not been studied. In this study, we show that, compared with wild-type mice, animals disrupted Hrh4 (H(4)RKO) develop more severe myelin oligodendrocyte glycoprotein (MOG)(35\x{2013}55)-induced encephalomyelitis. Mechanistically, determining frequency T (T(R)) cells secondary lymphoid tissues, regulates T(R) cell chemotaxis suppressor activity. Moreover, lack leads an impairment anti-inflammatory response due fewer during acute phase increase proportion Th17 cells.