| Large scale sequencing of transcripts from multiple sclerosis (MS) lesions has generated a number of unanticipated targets for modulating multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Surprisingly, a number of molecules associated with allergy and T helper 2 cells were identified, even though EAE and possibly MS are characterized as T helper 1 mediated diseases. This thesis investigates the role of two such molecules, histamine receptor type 1 (HIR) and platelet activating factor receptor (PAFR), in these diseases. We will show that signaling through histamine receptor type 1 modulates T cell reactivity and affects a number of other immune cells and that signaling through platelet activating factor receptor affects T cell and microglial function. In vivo, drugs that antagonize these receptors ameliorate EAE. Thus, these molecules and drugs represent a new avenue of study for intervention in multiple sclerosis. |
