title: Upregulation of miR-142-3p in peripheral blood mononuclear cells of operationally tolerant patients with a renal transplant.
abstract: Achieving drug-free tolerance or successfully using only small doses of immunosuppression is a major goal in organ transplantation. To investigate the potential mechanisms by which some kidney transplant recipients can achieve operational tolerance, we compared the expression profiles of microRNA in peripheral blood mononuclear cells of operationally tolerant patients with those of stable patients treated with conventional immunosuppression. B cells from operationally tolerant patients overexpressed miR-142-3p. The expression of miR-142-3p was stable over time and was not modulated by immunosuppression. In Raji B cells, overexpression of miR-142-3p modulated nearly 1000 genes related to the immune response of B cells, including potential miR-142-3p targets and molecules previously identified in the blood of operationally tolerant patients. Furthermore, our results suggested that a negative feedback loop involving TGF-β signaling and miR-142-3p expression in B cells may contribute to the maintenance of tolerance. In summary, miR-142-3p expression in peripheral blood mononuclear cells correlates with operational tolerance. Whether upregulation of miR-142-3p modulates inflammatory responses to promote tolerance or is a result of this tolerance state requires further study.
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale UMR643 and Institut de Transplantation Urologie, Néphrologie, Nantes, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Danger
authors.forename: Annaïck
authors.initials: A
authors.lastname: Pallier
authors.forename: Magali
authors.initials: M
authors.lastname: Giral
authors.forename: Marc
authors.initials: M
authors.lastname: Martínez-Llordella
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lozano
authors.forename: Nicolas
authors.initials: N
authors.lastname: Degauque
authors.forename: Alberto
authors.initials: A
authors.lastname: Sanchez-Fueyo
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouard
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011237:Predictive Value of Tests; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D023001:Transplantation Tolerance / Q000235:genetics* / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D035683:MicroRNAs; D016212:Transforming Growth Factor beta; C403126:MYLIP protein, human; D044767:Ubiquitin-Protein Ligases