Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS.
Histamine (HA), a biogenic amine with a broad spectrum of activities in both physiological and pathological settings, plays a key regulatory role in experimental allergic encephalomyelitis, the autoimmune model of multiple sclerosis. HA exerts its effect through four G protein-coupled receptors designated HA receptor H1, H2, H3, and H4. We report here that, compared with wild-type animals, mice with a disrupted HA H3 receptor (H3RKO), the expression of which is normally confined to cells of the nervous system, develop more severe disease and neuroinflammation. We show that this effect is associated with dysregulation of blood-brain barrier permeability and increased expression of MIP-2, IP-10, and CXCR3 by peripheral T cells. Our data suggest that pharmacological targeting of the H3R may be useful in preventing the development and formation of new lesions in multiple sclerosis, thereby significantly limiting the progression of the disease.
Teuscher
Cory
C
Departments of Medicine and Pathology, University of Vermont, Burlington, VT 05405, USA. c.teuscher@uvm.edu
Subramanian
Meena
M
Noubade
Rajkumar
R
Gao
Jian Feng
JF
Offner
Halina
H
Zachary
James F
JF
Blankenhorn
Elizabeth P
EP
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D004198:Disease Susceptibility / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018448:Models, Immunological; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D015398:Signal Transduction
D018100:Receptors, Histamine H3