All ETDs from UAB

Advisory Committee Chair

Alexander J Szalai

Advisory Committee Members

Scott R Barnum

Khurram Bashir

Peter H King

Hubert M Tse

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


C-reactive protein (CRP) is an acute phase reactant whose blood concentration rises in response all types of inflammation. And while CRP is widely used as a clinical marker of inflammation, it has several biological functions, e.g. activation of the classical complement cascade and binding Fcγ receptors in order to mediate multiple immune processes. The full extent of CRP’s physiological activities has not yet been fully elucidated, but there is significant evidence to establish that CRP plays an important role in the onset and progression of autoimmune disease. Seminal work from our lab showed that human CRP, hepatically expressed in transgenic mice, delays onset and decreases severity of experimental autoimmune encephalomyelitis (EAE), a rodent model of Multiple Sclerosis (MS) wherein myelin reactive (encephalitogenic) T cells that have escaped tolerance migrate to the CNS and mediate damage to myelinated axons. We subsequently demonstrated that this benefit of CRP relies upon engagement of the inhibitory Fc receptor, Fcγ receptor IIB (FcγRIIB). The objective of my research and of this report was to clarify CRP’s protection from in EAE by addressing two important questions: First, what is the identity of the FcγRIIB-expressing cell(s) to which CRP binds to protect mice from EAE?; Second, is expression of CRP in the CNS, rather than the liver, also sufficient to protect mice from EAE? Herein, we provide evidence that dendritic cells, an important FcγRIIB-expressing cell-type that presents antigen and therefore potently promotes generation of encephalitogenic T cells, are sufficient to support CRP’s protective actions in EAE. We also show that CRP can directly guide the fate of naive T cells, impacting their encephalitogenic potential, despite the fact that T cells do not express significant amounts of FcγIIB. Finally, we show that unlike its hepatically expressed counterpart, human CRP expressed in the CNS does not protect mice from EAE. In their sum, these data demonstrate that CRP can influence the immunological fate of encephalitogenic T cells both directly (via an as yet-unidentified proteinaceous receptor), and indirectly (via dendritic cells), providing an important conceptual framework for understanding the beneficial actions of CRP in CNS autoimmunity.



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