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TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis.
MedLine Citation:
PMID:  23207279     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In addition to its well-known pro-inflammatory effects, tumor necrosis factor (TNF) displays anti-inflammatory activities through mechanisms poorly understood. Previously, we reported the development of severe chronic Yersinia enterocolitica-induced reactive arthritis (ReA) in mice lacking the TNF receptor (TNFR)p55. As regulatory T (T(reg)) cells limit chronic inflammation, here we aim to investigate the expansion and function of CD4(+)CD25(+)FoxP3(+) T(reg) cells in the ReA animal model. The number of T(reg) cells as well as the FoxP3 mRNA expression and interleukin (IL)-10 levels were significantly decreased in joint regional lymph nodes (RLNs) of TNFRp55(-/-) mice vs wild-type (WT) mice at the arthritis onset. However, at chronic phase of arthritis, the number of T(reg) cell in TNFRp55(-/-) was similar to WT mice. To explore the in vivo function of T(reg) cells at this chronic phase in WT and TNFRp55-deficient mice, we adoptively transferred CD4(+) T cells from TNFRp55-deficient mice of day 21, into naïve WT or TNFRp55(-/-) mice. When knockout mice were used as recipients we observed higher delayed-type hypersensitivity (DTH) responses and joint inflammation after heat-killed Yersinia (HKY) stimulation. Accordingly, we found higher levels of IL-17, interferon (IFN)-γ, IL-6, transforming growth factor (TGF)-β1 and IL-12/23p40 and lower IL-10 levels in RLN of paws challenged with HKY in TNFRp55(-/-) recipient mice. In addition, we found that CD4(+) T cells from TNFRp55(-/-) mice controlled antigen-specific IL-12/23(p40) production in recipient WT mice. Our results show that TNFRp55 controls the induction and function of T(reg) cells through differential regulation of cytokine production, suggesting a novel molecular target for immune intervention in ReA.Immunology and Cell Biology advance online publication, 4 December 2012; doi:10.1038/icb.2012.65.
Authors:
Ethelina Cargnelutti; José L Arias; Susana R Valdez; Gabriel A Rabinovich; María S Di Genaro
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-04
Journal Detail:
Title:  Immunology and cell biology     Volume:  -     ISSN:  1440-1711     ISO Abbreviation:  Immunol. Cell Biol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8706300     Medline TA:  Immunol Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Immunology, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis; Laboratory of Immunopathology, Multidisciplinary Institute of Biological Investigations-San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations (CONICET), San Luis, Argentina.
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