Antimicrobial Proteins and Peptides and Immune Disease
Rheumatologists are well acquainted with the acquired (HLA-DR dependent) and innate (HLA-DR independent) arms of the immune system. Most of the recent attention on the innate immune system has derived from recognition of Toll receptors expressed on dendritic and other cells that play a role in instruction of B-cells, T-cells, and release of cytokines such as type I interferon. However, other defense factors such as C-reactive protein and complement are part of the innate system's response to "danger." The antimicrobial proteins and peptides should be considered as part of that immediate response, and their activity plays a role in immune disorders.
Defensins have been most clearly studied for their role in inflammatory bowel disease (IBD). For example, linkage studies of members of multiply affected kindreds have identified a number of genomic areas of linkage with IBD, including putative IBD genes ("IBD1") that have been identified as encoders for the nucleotide-binding oligomerization domain protein 2 (NOD2), which is a sensor for bacterial muramyl dipeptide.
Activation of NOD2 stimulates expression of alpha-defensins and promotes cytokine and chemokine production by immunocytes. Defective NOD2 signaling pathway and impaired expression of defensins are linked to the pathogenesis of Crohn's disease, to instruct adaptive immune response in the gut micro-environment.
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