title: Functional improvement of regulatory T cells from rheumatoid arthritis subjects induced by capsular polysaccharide glucuronoxylomannogalactan.
abstract: OBJECTIVE
  Regulatory T cells (Treg) play a critical role in the prevention of autoimmunity, and the suppressive activity of these cells is impaired in rheumatoid arthritis (RA). The aim of the present study was to investigate function and properties of Treg of RA patients in response to purified polysaccharide glucuronoxylomannogalactan (GXMGal).
  
  
  METHODS
  Flow cytometry and western blot analysis were used to investigate the frequency, function and properties of Treg cells.
  
  
  RESULTS
  GXMGal was able to: i) induce strong increase of FOXP3 on CD4+ T cells without affecting the number of CD4+CD25+FOXP3+ Treg cells with parallel increase in the percentage of non-conventional CD4+CD25-FOXP3+ Treg cells; ii) increase intracellular levels of TGF-β1 in CD4+CD25-FOXP3+ Treg cells and of IL-10 in both CD4+CD25+FOXP3+ and CD4+CD25-FOXP3+ Treg cells; iii) enhance the suppressive activity of CD4+CD25+FOXP3+ and CD4+CD25-FOXP3+ Treg cells in terms of inhibition of effector T cell activity and increased secretion of IL-10; iv) decrease Th1 response as demonstrated by inhibition of T-bet activation and down-regulation of IFN-γ and IL-12p70 production; v) decrease Th17 differentiation by down-regulating pSTAT3 activation and IL-17A, IL-23, IL-21, IL-22 and IL-6 production.
  
  
  CONCLUSIONS
  These data show that GXMGal improves Treg functions and increases the number and function of CD4+CD25-FOXP3+ Treg cells of RA patients. It is suggested that GXMGal may be potentially useful for restoring impaired Treg functions in autoimmune disorders and for developing Treg cell-based strategies for the treatment of these diseases.
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Pericolini
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gabrielli
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Alunno
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bartoloni Bocci
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Perito
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, New York, United States of America.
authors.forename: Siu-Kei
authors.initials: SK
authors.lastname: Chow
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Cenci
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, New York, United States of America.
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gerli
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Vecchiarelli
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D011134:Polysaccharides