title: Inhibition of Experimental Autoimmune Encephalomyelitis in Human C-Reactive Protein Transgenic Mice Is FcγRIIB Dependent.
abstract: We showed earlier that experimental autoimmune encephalomyelitis (EAE) in human C-reactive protein (CRP) transgenic mice (CRPtg) has delayed onset and reduced severity compared to wild-type mice. Since human CRP is known to engage Fc receptors and Fc receptors are known to play a role in EAE in the mouse, we sought to determine if FcγRI, FcγRIIb, or FcγRIII was needed to manifest human CRP-mediated protection of CRPtg. We report here that in CRPtg lacking either of the two activating receptors, FcγRI and FcγRIII, the beneficial effects of human CRP are still observed. In contrast, if CRPtg lack expression of the inhibitory receptor FcγRIIB, then the beneficial effect of human CRP is abrogated. Also, subcutaneous administration of purified human CRP stalled progression of ongoing EAE in wild-type mice, but similar treatment failed to impede EAE progression in mice lacking FcγRIIB. The results reveal that a CRP → FcγRIIB axis is responsible for protection against EAE in the CRPtg model.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, 1825 University Boulevard, SHEL 214, Birmingham, AL 35294-2182, USA.
authors.forename: Xian-Zhen
authors.initials: XZ
authors.lastname: Hu
authors.forename: Tyler T
authors.initials: TT
authors.lastname: Wright
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Jones
authors.forename: Theresa N
authors.initials: TN
authors.lastname: Ramos
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Skibinski
authors.forename: Mark A
authors.initials: MA
authors.lastname: McCrory
authors.forename: Scott R
authors.initials: SR
authors.lastname: Barnum
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Szalai