A Key Role for Inhibins in Dendritic Cell Maturation and FunctionReport as inadecuate




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Inhibins are members of the TGFβ superfamily, which regulate many cellular processes including differentiation, proliferation, survival and apoptosis. Although initially described as hormones regulating the hypothalamus-pituitary-gonadal axis, based on their ability to antagonize Activins, our group has recently reported that they play a role in thymocyte differentiation and survival, as well as in thymic stromal cell maturation and nTreg generation. Here, we used Inhibin knock out mice Inhα- to investigate the role of Inhibins in peripheral dendritic cell maturation and function. We first demonstrated that LPS treated Inhα+-+ bone marrow derived dendritic cells BMDC were capable to produce significant levels of Inhibin A. Interestingly, Inhα- BMDC showed reduced MHCII and CD86 upregulation and increased PD-L1 expression in response to LPS compared to Inhα+-+, which correlated with reduced ability to induce proliferation of allogeneic T cells. The -semi-mature- phenotype displayed by Inhα- mBMDC correlated with increased levels of IL-10 and slightly decreased IL-6 production after LPS stimulation. In addition, Inhα- mBMDC showed impaired migration towards CCL19 and CCL21, assessed by in vitro chemotaxis and in vivo competitive homing experiments, despite their normal CCR7 expression. Furthermore, in vivo LPS-induced DC maturation was also diminished in Inhα- mice, specially within the LC CD207+ CD11b+ CD103- subpopulation. Finally, analysis of delayed type hypersensitivity responses in Inhα- mice, showed reduced ear swelling as a result of reduced cellular infiltration in the skin, correlating with impaired homing of CD207+ DCs to the draining lymph nodes. In summary, our data demonstrate for the first time that Inhibins play a key role in peripheral DC maturation and function, regulating the balance between immunity and tolerance.



Author: Roxana Olguín-Alor, Marisol de la Fuente-Granada, Laura C. Bonifaz, Laura Antonio-Herrera, Eduardo A. García-Zepeda, Gloria Sol

Source: http://plos.srce.hr/



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