Anti-LGMN polyclonal antibody [Biotin]

In vitro fertilization has overcome infertility issues for many couples. However, achieving implantation of a viable embryo into the maternal endometrium remains a limiting step in optimizing pregnancy success. The molecular mechanisms which characterize the transient state of endometrial receptivity, critical in enabling embryo-endometrial interactions, and proteins which underpin adhesion at the implantation interface, are limited in humans despite these temporally regulated processes fundamental to life. Hence, failure of implantation remains the "final frontier" in infertility. A human coculture model is utilized utilizing spheroids of a trophectoderm (trophoblast stem) cell line, derived from pre-implantation human embryos, and primary human endometrial epithelial cells, to functionally identify "fertile" versus "infertile" endometrial epithelium based on adhesion between these cell types. Quantitative proteomics identified proteins associated with human endometrial epithelial receptivity ("epithelial receptome") and trophectoderm adhesion ("adhesome"). As validation, key "epithelial receptome" proteins (MAGT-1/CDA/LGMN/KYNU/PC4) localized to the epithelium of receptive phase (mid-secretory) endometrium obtained from fertile, normally cycling women but is largely absent from non-receptive (proliferative) phase tissues. Factors involved in embryo-epithelium interaction in successive temporal stages of endometrial receptivity and implantation are demonstrated and potential targets for improving fertility are provided, enhancing potential to become pregnant either naturally or in a clinical setting.

Autocrine activation of the complement receptors C3aR and CD46 by complement activation components C3a and C3b produced through C3 cleavage by the protease cathepsin L (CTSL) during T cell stimulation is a requirement for IFN-gamma production and Th1 induction in human CD4(+) T cells. Thus, lack of autocrine CD46 activation, such as in CD46-deficient patients, is associated with defective Th1 responses and recurrent infections. We have identified LGMN [the gene coding for legumain, also known as asparaginyl endopeptidase (AEP)] as one of the key genes induced by CD46 co-stimulation during human CD4(+) T cell activation. AEP processes and activates a range of proteins, among those alpha 1-thymosin and CTSL, which both drive intrinsically Th1 activity-but has so far not been described to be functionally active in human T cells. Here we found that pharmacological inhibition of AEP during activation of human CD4(+) T cells reduced CTSL activation and the CTSL-mediated generation of intracellular C3a. This translated into a specific reduction of IFN-gamma production without affecting cell proliferation or survival. In line with these findings, CD4(+) T cells isolated from Lgmn(-/-) mice also displayed a specific defect in IFN-gamma secretion and Th1 induction. Furthermore, we did not observe a role for AEP-driven autocrine alpha 1-thymosin activation in T cell-derived IFN-gamma production. These data suggest that AEP is an "upstream" activator of the CTSL-C3-IFN-gamma axis in human CD4(+) T cells and hence an important supporter of human Th1 induction.