Tolerance and immunity to the inducible self antigen C-reactive protein in transgenic mice

C-reactive protein, or CRP, is an acute phase protein (1, 2) synthesized and released from the liver (3). CRP is transcriptionally induced during systemic inflammatory responses (1, 2). CRP expression in the thymus has previously been reported but in the context of promiscuous gene expression of self-antigen during negative selection (4, 5) or after ectopic expression (6). Here, by comparing the transcriptomes of mTEC and cTEC from the thymuses of mice at 1, 3 and 6 months using a published dataset (7), we found that CRP was among the genes whose expression changed most significantly between cTEC and mTEC at 3 months of murine life. CRP was expressed at significantly higher amounts in mTEC compared to cTEC. Thus, CRP, a molecule typically thought of as expressed by the liver and induced during systemic inflammatory responses, is expressed in a cell-type specific manner during mammalian development in the thymus.

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Inhibition of Experimental Autoimmune Encephalomyelitis in Human C-Reactive Protein Transgenic Mice Is FcRIIB Dependent

Autoimmune Diseases ◽

10.4061/2011/484936 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Xian-Zhen Hu ◽

Tyler T. Wright ◽

Nicholas R. Jones ◽

Theresa N. Ramos ◽

Gregory A. Skibinski ◽

...

Keyword(s):

Experimental Autoimmune Encephalomyelitis ◽

Transgenic Mice ◽

Fc Receptors ◽

Subcutaneous Administration ◽

Wild Type ◽

C Reactive Protein ◽

Autoimmune Encephalomyelitis ◽

Similar Treatment ◽

Reactive Protein ◽

Experimental Autoimmune

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 FcRI, FcRIIb, or FcRIII was needed to manifest human CRP-mediated protection of CRPtg. We report here that in CRPtg lacking either of the two activating receptors, FcRI and FcRIII, the beneficial effects of human CRP are still observed. In contrast, if CRPtg lack expression of the inhibitory receptor FcRIIB, 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 FcRIIB. The results reveal that a axis is responsible for protection against EAE in the CRPtg model.

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Hepatic but Not CNS-Expressed Human C-Reactive Protein Inhibits Experimental Autoimmune Encephalomyelitis in Transgenic Mice

Autoimmune Diseases ◽

10.1155/2015/640171 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Tyler T Wright ◽

Rachel V. Jimenez ◽

Todd E. Morgan ◽

Namrata Bali ◽

Xiaogang Hou ◽

...

Keyword(s):

Experimental Autoimmune Encephalomyelitis ◽

Transgenic Mice ◽

Gene Promoter ◽

C Reactive Protein ◽

Autoimmune Encephalomyelitis ◽

Reactive Protein ◽

Protective Actions ◽

Dependent Protein ◽

Low Levels ◽

Experimental Autoimmune

We recently demonstrated that human C-reactive protein (CRP), expressed hepatically in transgenic mice (CRPtg), improved the outcome of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The liver is the primary site of CRP synthesis in humans and in CRPtg mice but is also expressed by both at low levels in the CNS. To determine if CNS expression of human CRP is sufficient to impact EAE, we generated neuronal CRP transgenic mice (nCRPtg) wherein human CRP expression is driven by the neuron-specific Ca2+/calmodulin-dependent protein kinase IIα(CaMKIIα) gene promoter. We found that hepatically expressed/blood-borne CRP, but not CNS expressed CRP, lessened EAE severity. These outcomes indicate that the protective actions of human CRP in EAE are manifested in the periphery and not in the CNS and reveal a previously unappreciated site specificity for the beneficial actions of CRP in CNS disease.

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