title: Impact of mycophenolic acid and tacrolimus on Th17-related immune response.
abstract: BACKGROUND
  Little is known on the impact of immunosuppressive drugs on the development of the different T-cell subsets that compose the immune balance. We have explored the influence of mycophenolic acid (MPA) and tacrolimus on T cells response with a special focus on the Th17-cell subset.
  
  
  METHODS
  In an in vitro model of human CD4 cells activation, we first compared the influence of MPA and tacrolimus on the transcription of different set of genes related to each of the main T-cell subsets and then investigated how these two drugs interfere with interleukin (IL)-17 production. We also studied, in stable kidney transplant patients, the relation between IL-17 serum concentration and systemic drug exposure.
  
  
  RESULTS
  MPA and tacrolimus exhibited a comparable impact on T-cell response, dampening most Th1-related genes transcription and preserving regulatory T cells/Th2 molecular phenotypes. Although both MPA and tacrolimus decreased Th17-related transcripts after T-cell activation, MPA exerted a stronger inhibitory effect on IL-17 production than tacrolimus. Accordingly, renal transplant patients treated with MPA in combination with minimized dose of tacrolimus tended to have lower circulating IL-17 levels than patients treated with tacrolimus alone given at conventional dose.
  
  
  CONCLUSIONS
  A treatment combining MPA and tacrolimus is susceptible to favorably tip the immune balance and might confer optimal allograft immunoprotection. Because of its ability to profoundly inhibit IL-17 production, MPA may help to better overcome Th17-related alloreactivity in the context of calcineurin inhibitor-minimizing protocol.
authors.affiliation: Laboratoire de Néphrologie, Université Jean Monnet, and Service de Néphrologie, Dialyse et Transplantation rénale, Hôpital Nord, CHU de Saint-Etienne, France.
authors.forename: Farida
authors.initials: F
authors.lastname: Abadja
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Atemkeng
authors.forename: Eric
authors.initials: E
authors.lastname: Alamartine
authors.forename: François
authors.initials: F
authors.lastname: Berthoux
authors.forename: Christophe
authors.initials: C
authors.lastname: Mariat
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D020381:Interleukin-17 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology*; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D009173:Mycophenolic Acid; D016559:Tacrolimus