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FRI0010 Effects of leptin and adiponectin on proliferation, activation and th17 differentiation were significantly increased in cd4+ t cells from rheumatoid arthritis patients
  1. C. BustosRivera_Bahena1,
  2. D. Xibille-Friedmann2,
  3. M. Sandoval-Rios1,
  4. J.-L. Montiel-Hernandez1
  1. 1Facultad de Farmacia, Universidad Autonoma del Estado de Morelos
  2. 2Dept Rheumatology, Hospital General de Cuernavaca, Cuernavaca, Mexico

Abstract

Background Recent in vitro and in vivo studies suggest that leptin and adiponectin are involved in the development of the inflammatory profile of rheumatoid arthritis (RA) patients. Previous findings by our group have shown that levels of these adipokines are significantly higher in RA patients, correlate with variations in DAS28 after two years of follow-up and baseline levels of adiponectin seems to predict the DMARD treatment response. However, the biological mechanism of leptin and adiponectin on T cell physiology is still poorly known.

Objectives To compare the in vitro proliferative, activation and TH17 differentiation effects of leptin and adiponectin on mononuclear (MN) and CD4+ T cells from healthy donors and RA patients.

Methods All RA patients included in the present study fulfilled the ACR 2010 criteria, signed an informed consent form and were followed at the rheumatology clinic. Healthy donors samples were obtained from a local blood bank. Mononuclear cells were obtained by Ficoll Paque and CD4+ T cells were magnetically purified. In vitro assays were done employing recombinant human leptin and adiponectin. Proliferation was evaluated by MTT technique. Activation was evaluated by flow cytometry (CD25, CD69) and by ELISA (IL-1β, IL-2, IL-6, TNF). TH17 differentiation was evaluated by ELISA/cytometry (IL-17A/E) and western blot (RORγT). Descriptive statistics was employed to evaluate differences between groups and Spearman correlation was used to associate them with clinical parameters.

Results MN and CD4+T cells from RA patients showed a higher proliferative effect when exposed to leptin and adiponectin in comparison with healthy donors. Interesting, the level of proliferation correlated with the DAS28 of patients. Similarly, cells from patients were more sensitive to leptin and adiponectin treatment when evaluating CD25+/CD69+ cell expression and IL-2, TNF secretion, in comparison to healthy donor cells. Comparatively, adiponectin treatment was more effective to induce the expression of CD25, CD69 and IL-6, whereas leptin was a better inductor of IL-2 and TNF-a on the RA patient cells. Comparing this with the clinical activity of patients, we only observed a significant correlation between the DAS28 and the IL-2 induction when exposed to leptin. Preliminary assays showed that leptin was also capable to rescue MN cells from an apoptotic environment by a mechanism related to IL-2 secretion. On the other hand, MN cells from RA patients incubated for several days with leptin induced an increase of IL-6 and TGF-β in the cell culture supernatant and cell expression of RORγT, suggesting a direct mechanism by which high levels of leptin could favors inflammatory disorders as RA. At present, we are comparing the leptin and adiponectin receptor levels and signaling pathways to explain the differences observed between cells derived from healthy donors and RA patients.

Conclusions MN and CD4+ T cells derived from RA patients were more sensitive to leptin or adiponectin treatment, in comparison to healthy donor cells, with respect to their effects on proliferation, activation and TH17 differentiation. Additionally, clinical activity was correlated with the proliferative effect and IL-2 secretion induced by treatment with leptin.

Acknowledgements This work was supported by grant from SEP/CONACYT CB-2010 (#155392).

Disclosure of Interest None Declared

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