PERSONAL DE APOYO
BAZ Placida
congresos y reuniones científicas
Título:
The association of IL-6 and human Treg with a successful pregnancy
Autor/es:
ARRUVITO LOURDES; PANDOLFI JULIETA; BAZ PLÁCIDA; BILLORDO LUIS ARIEL
Lugar:
Buenos Aires
Reunión:
Simposio; 3rd Latin American Symposium of Reproductive Immunology and 1st Latin American ASRI Satellite Symposium; 2011
Resumen:
Interleukin 6 (IL-6) has been implicated in the pathogenesis of many autoimmune and chronic inflammatory diseases and as described above, this cytokine is increased in RSA patients. Furthermore, IL-6 has been reported to modulate Tregs. However, despite the role assigned to IL- 6 in Tregs, little is known about the mechanism by which IL-6 modulates this cell type. During the classical pathway of IL-6 signaling, IL-6 first binds to the membrane IL-6 receptor (IL-6R) and the complex of IL-6/IL-6R associates with the signal-transducing membrane protein gp130 promoting its dimerization and the subsequent initiation of intracellular signals. Whereas the expression of IL-6R is restricted, gp130 is expressed by most if not all cells in the body. Alternatively, in the so called trans-signaling process, soluble forms of the IL-6R (sIL-6R) are capable of forming a complex with IL-6 and of stimulating cells which only express gp130. Soluble forms of sIL-6R and soluble gp130 (sgp130) are naturally present in serum and in several fluids. The process of trans-signaling can be inhibited by a molar excess of sgp130. Our study of the impact of IL-6 trans-signaling in women suffering from RSA indicated that in contrast with control women, sera from RSA women contained factors that induced an enhanced mixed lymphocyte reaction when stimulated with paternal PBMCs. Sera that induced the MLR-enhanced effect showed an imbalance in the levels of soluble components of IL-6 trans-signaling pathway. In comparison with fertile women, those with RSA showed significantly increased levels of soluble IL-6 receptor and IL-6, and decreased levels of the trans-signaling inhibitor (sgp130). In addition, it was reported that activation of naïve CD4+ T cells or isolated nTregs with IL-2 and TGF-beta down- regulated IL-6 receptor expression and its signaling pathway, and caused them to become resistant to Th17 conversion.In Summary: 1-We explored the cause of the diminished expansion of Tregs in RSA patients. 2-The expression of FOXP3 on PBMC detected above baseline before anycell division occurs, indicated that cells did not previously express FOXP3. 3-RSA patients showed limited secretion of IL-2 and TGF-beta cytokines involved in the differentiation of iTreg from naive CD4+CD25- 4-Defects in IL-2/STAT5 signaling pathway in CD4+CD25+FOXP3+ Treg cells from RSA women contribute to lower generation and persistence of FOXP3 expression and a lower suppressor activity that might impact on establishment of maternal tolerance. 5-IL-6, known to modulate Treg, and implicated in the pathogenesis of many autoimmune diseases, was also found increased in RSA women, and seems to abrogate the suppressor effect of iTreg cells.enviar mensaje