TUMOR NECROSIS FACTOR RECEPTOR p55 SIGNALING INFLUENCES REGULATORY T CELLS FREQUENCY IN YERSINIA-INDUCED REACTIVE ARTHRITIS

ETHELINA CARGNELUTTI; JOSÉ L. ARIAS1; SUSANA R. VALDEZ2; GABRIEL A. RABINOVICH; MARÍA SILVIA DI GENARO

Lima

Congreso; Inmunopeu 2012; 2012

Asociación Latinoamericana de Inmunologia (ALAI)

We have demonstrated that TNF receptor p55 knockout (KO) mice develop severe Y. enterocolitica (Ye) induced-reactive arthritis (ReA). The aim was to study the regulatory T (Treg) cells in this ReA model. Knockout and WT mice were orally infected with Ye. After 7, 14 and 21 days, Treg cells frequencies in regional lymph nodes (RLN) and mesenteric lymph nodes (MLN) were determined by flow cytometry. CD4+ T cells were adoptively transferred from infected KO mice into naïve KO or WT mice. Delayed-type hypersensitive (DTH) was evaluated after intra-plantar heat-killed Yersinia (HKY) or PBS injection. Ankle joints were used to histological evaluation; and RLN to cytokine analysis by ELISA. We could not find significant differences in Treg cell frequency in MLN. In RLN, 14 days after infection, KO mice showed lower frequency of Treg cells compared to WT mice (p<0.05). In contrast, at 21 days, KO mice increased Treg cells frequency in RLN (p<0.05). Recipient KO mice showed higher DTH and joint inflammation after HKY challenge. This was in line with higher IL-17, IFN-γ, IL-6, TGF-β1 and IL-12/IL-23p40 and lower IL-10 levels in RLN from paws of recipient KO mice receiving HKY. Our results suggest that TNFRp55 signaling controls the induction and function of Treg cells through differential regulation of cytokine environment.