Abstract
Galectin-1 (Gal-1) is a pleiotropic lectin involved in the modulation of immune responses. Using a model of rat experimental autoimmune orchitis (EAO), we investigated the role of Gal-1 in testicular inflammation. EAO is characterized by leukocytic infiltrates in the interstitium, damage of spermatogenesis and production of inflammatory mediators like TNFα and MCP1 causing infertility. In normal rat testis Gal-1 was mainly expressed in Sertoli cells and germ cells. In the inflamed testis, Gal-1 expression was significantly downregulated most likely due to germ cell loss. Analyses of lectin binding and expression of glucosaminyl- and sialyltransferases indicated that the glycan composition on the cell surface of Sertoli and peritubular cells becomes less favourable for Gal-1 binding under inflammatory conditions. In primary Sertoli cells Gal-1 expression was found to be upregulated after TNFα challenge. Pretreatment with Gal-1 synergistically and specifically enhanced TNFα-induced expression of MCP1, IL-1α, IL-6 and TNFα in Sertoli cells. Combined stimulation of Sertoli cells with Gal-1 and TNFα enhanced the phosphorylation of MAP kinases as compared to TNFα or Gal-1 alone. Taken together, our data show that Gal-1 modulates inflammatory responses in Sertoli cells by enhancing the pro-inflammatory activity of TNFα via stimulation of MAPK signalling.
Highlights
Infertility and subfertility affect 10–15% of couples and approximately 50% of cases are caused either by factors associated with the male alone or in combination with the female[1]
Because the ratio of testicular cell types is changed in Experimental autoimmune orchitis (EAO) testis due to the loss of germ cells and infiltration of immune cells, the relative expression of Gal-1 mRNA was normalized to the Sertoli cell specific transcript Sox[9] (Fig. 2d)
An increasing body of evidence indicates that Gal-1 has immunoregulatory functions in autoimmune disease models including systemic lupus erythematosus[33], lysolecithin-induced demyelination[34] and experimental autoimmune encephalomyelitis (EAE)[35] through mechanisms like selective induction of Th1 and Th17 cell apoptosis, inhibition of T cell trafficking, expansion of tolerogenic dendritic cells and regulatory T cells
Summary
Infertility and subfertility affect 10–15% of couples and approximately 50% of cases are caused either by factors associated with the male alone or in combination with the female[1]. Experimental autoimmune orchitis (EAO) is a rodent model for studying organ-specific autoimmunity and chronic testicular inflammation that reproduces pathological changes seen in some cases of human immunological infertility[10,11,12]. Through binding to specific glycan structures, Gal-1 is involved in a variety of physiologic and pathologic processes including pathogen recognition, selective induction of Th1 and Th17 apoptosis[22], inhibition of T cell trafficking[23], expansion of tolerogenic dendritic cells and regulatory T cells[24,25], maintenance of maternal-fetal www.nature.com/scientificreports/. We investigated the expression of Gal-1 in rat EAO testis and the ability of Gal-1 to induce an inflammatory response in Sertoli cells. The glycan profiles in EAO testes and TNFα challenged Sertoli as well as peritubular cells were investigated by using lectin binding assays
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