INQUISAL   20936
INSTITUTO DE QUIMICA DE SAN LUIS "DR. ROBERTO ANTONIO OLSINA"
Unidad Ejecutora - UE
artículos
Título:
TNFRp55 deficiency augments Th17 response during development of arthritis.
Autor/es:
RICARDO J. ELIÇABE; ETHELINA CARGNELUTTI; MARÍA I. SERER; PATRICIA W. STEGE; SUSANA R. VALDEZ; MARTA A. TOSCANO; GABRIEL A. RABINOVICH; MARÍA S. DI GENARO
Revista:
JOURNAL OF IMMUNOLOGY
Editorial:
AMER ASSOC IMMUNOLOGISTS
Referencias:
Año: 2010 vol. 185 p. 4485 - 4495
ISSN:
0022-1767
Resumen:
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Reactive arthritis (ReA) is a type of arthritis originated from certain gastrointestinal or genitourinary infections. In previous studies we reported the development of progressive Yersiniaenterocolitica-induced ReA in mice lacking TNF receptor p55 (TNFRp55); yet the mechanisms underlying this effect are still uncertain. Here we investigated the impact of TNFRp55 deficiency in modulating antigen-specific Th1 and Th17 responses during this arthritogenic process. We found higher severity of ReA in TNFRp55-/- mice compared with their wild-type (WT) counterparts. This effect was accompanied by increased levels of Yersinia LPS in the joints of knockout mice. Analysis of the local cytokine profile revealed higher amounts of IFN-g and IL-17 in arthritic joints of TNFRp55-/- compared to WT mice at day 21 after infection. Moreover, altered IL-17 and IFN-γ production was observed in mesenteric and inguinal lymph nodes of Yersinia-infected TNFRp55-/-mice, and in spleen cells obtained from infected mice and restimulated ex vivo with bacterial antigens. Increased levels of cytokine secretion were associated to higher frequency of CD4+IL-17+, CD4+IFN-g+ and IL-17+IFN-g+ cells in TNFRp55-/- compared to WT mice. Remarkably, antibody-mediated blockade of IL-17 and/or IFN-g resulted in reduced joint histological scores in TNFRp55-/- mice. A mechanistic analysis revealed the involvement of p40, a common subunit of heterodimeric IL-12 and IL-23 in the generation of augmented IFN-g and IL-17 production under TNFRp55 deficiency. Taken together, these data indicate that, in the absence of TNFRp55 signaling, Th1 and Th17 effector cells, may act in concert to sustain the inflammatory response in bacterial-induced arthritogenic processes.