The filarial nematode product, ES-62 targets IL-22 to mediate protection in collagen-induced arthritis (P5212)

Abstract

Abstract Parasitic worms skew immune responses to a Th2-like phenotype, inhibiting Th1/Th17 pathways and expanding regulatory cells such as Tregs. Worms can achieve such immunoregulation by secreting specific products like ES-62, a glycoprotein secreted by the filarial nematode A. viteae. We have previously shown ES-62 to be protective in Collagen-Induced Arthritis, a murine model of rheumatoid arthritis, and that the mechanism associated with protection involves a down-regulation of the cytokine IL-17. We have now analyzed the effects of ES-62 on other Th17-related cytokines focusing on IL-22, a cytokine that has been reported to exhibit both pro and anti-inflammatory actions in animal models of inflammatory disease. In CIA, administration of ES-62 appears to target the IL-17/IL-22 balance in lymph nodes and joints of animals resulting in modulation of the number and inflammatory phenotype of infiltrating and resident cells in the joint, and consequent attenuation of inflammation. Interestingly, using a combination of recombinant IL-22 and blocking antibody in in vivo studies, the precise type of effect of IL-22 on CIA progression was shown to depend largely both on the location of IL-22 action and also the stage at which the cytokine is produced during disease progression. These findings have allowed us to identify a novel mechanism used by the helminth product ES-62 to reduce autoimmune arthritis and they also contribute to our understanding of the complex biology of IL-22