Yersinia enterocolitica-INDUCED REACTIVE ARTHRITIS: ANIMAL MODEL IN TNFRp55-/- MICE AND HUMAN STUDIES

ELICABE, JAVIER; CARGNELUTTI, ETHELINA; LACOSTE, MARÍA GABRIELA; RABINOVICH, GABRIEL ADRIÁN; DI GENARO, MARÍA SILVIA

Buenos Aires

Congreso; First French - Argentine Immunology Congress, LVIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI), XIII Jornada Científica del Grupo Rioplatense de Citometría de Flujo (GRCF) y 3° Jornadas Argentinas de Inmunodeficiencias Primarias (SAP); 2010

SAI, GRCF, SFI y SAP

An episode of acute enteric infection can lead to complications and trigger chronic disease such as reactive arthritis (ReA). Yersiniosis is a zoonotic foodborne associated with a risk ReA. It belongs to the group of arthritidies known as the spondyloarthropathies (SpA). The pathogenesis of ReA is incompletely understood. We have studied the development of ReA after Yersinia enterocolitica oral infection in mice lacking TNF receptor p55 (TNFRp55-/-) and found higher severity of ReA in TNFRp55-/- compared with wild-type (WT) mice. Analysis of articular cytokine profile revealed higher amounts of IFN-g and IL-17 in TNFRp55-/-. Accordingly, IL-17 levels were increased in synovial fluids of SpA compared with control osteoarthritis patients. Moreover, TNFRp55-/- mice presented higher frequency of CD4+ IL-17+, CD4+ IFN-γ+ and IL-17+ IFN-γ+ cells. In addition, antibody mediated blockade of IL-17 and/or IFN- γ resulted in reduced joint histological scores in TNFRp55-/- mice. Interestingly, local p40, a common subunit of IL-12 and IL-23, augmented under TNFRp55 deficiency. Moreover, higher p40, oxide nitric and IL-6 were secreted by Yersinia LPS-stimulated TNFRp55-/- macrophages. We concluded that TNFRp55 may modulate macrophage functions in response to Yersinia components, and that, in the absence of TNFRp55 signaling, Th1 and Th17 effector cells, may act in concert to sustain ReA.