Lipopolysaccharide pretreatment increases the sensitivity of the TRPV1 channel and promotes an anti-inflammatory phenotype of capsaicin-activated macrophages.

BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) is well-established in neuronal function, yet its role in immune reactions remains enigmatic. The conflicting data on its inflammatory role, suggesting both pro-inflammatory and anti-inflammatory effects upon TRPV1 stimulation in immune cells, adds complexity. To unravel TRPV1 immunomodulatory mechanisms, we investigated how the TRPV1 agonist capsaicin influences lipopolysaccharide (LPS)-induced pro-inflammatory macrophage phenotypes. RESULTS: Changes in the surface molecules, cytokine production, and signaling cascades linked to the phenotype of M1 or M2 macrophages of the J774 macrophage cell line and bone marrow-derived macrophages, treated with capsaicin before or after the LPS-induced inflammatory reaction were determined. The functional capacity of macrophages was also assessed by infecting the stimulated macrophages with the intracellular parasite Leishmania mexicana. CONCLUSION: Our findings reveal that TRPV1 activation yields distinct macrophage responses influenced by the inflammatory context. LPS pre-treatment followed by capsaicin activation prompted increased calcium influx, accompanied by a shift toward an anti-inflammatory M2b-like polarization state.

Xenogeneic Sertoli cells modulate immune response in an evolutionary distant mouse model through the production of interleukin-10 and PD-1 ligands expression.

BACKGROUND: Immunomodulatory mechanisms of Sertoli cells (SCs) during phylogeny have not been described previously. This study attempted to reveal mechanisms of SC immune modulation in an evolutionary distant host. METHODS: The interaction of the SC cell line derived from Xenopus tropicalis (XtSC) with murine immune cells was studied in vivo and in vitro. The changes in the cytokine production, the intracellular and surface molecules expression on murine immune cells were evaluated after co-culturing with XtSCs. Migration of XtSCs in mouse recipients after intravenous application and subsequent changes in spleen and the testicular immune environment were determined by flow cytometry. RESULTS: The in vitro co-culture model was established, allowing the study of XtSCs interaction with murine immune cells. Intracellular staining of interleukin (IL-)10 revealed a significant increase in its expression in macrophages and B cells co-cultured with XtSCs, compared to both unstimulated cells and xenogeneic control. On the contrary, a significant decrease in Th lymphocytes expressing interferon-gamma was observed. The expression of both PD-1 ligands (PD-L1 and PD-L2) was upregulated on the macrophage surfaces after co-culture with XtSCs, but not with the controls. XtSCs migrated specifically to testes when administered intravenously and modulated systemic and local testicular microenvironment; this was detected by the expression of molecules associated with suppressive phenotype by CD45+ cells in both spleen and testes. CONCLUSION: We have demonstrated for the first time that SCs can migrate and modulate immune response in a phylogenetically distant host. It was further observed that SCs induce expression of molecules associated with immunosuppression, such as IL-10 and PD-1 ligands.

Sertoli Cells Possess Immunomodulatory Properties and the Ability of Mitochondrial Transfer Similar to Mesenchymal Stromal Cells.

It is becoming increasingly evident that selecting an optimal source of mesenchymal stromal cells (MSCs) is crucial for the successful outcome of MSC-based therapies. During the search for cells with potent regenerative properties, Sertoli cells (SCs) have been proven to modulate immune response in both in vitro and in vivo models. Based on morphological properties and expression of surface markers, it has been suggested that SCs could be a kind of MSCs, however, this hypothesis has not been fully confirmed. Therefore, we compared several parameters of MSCs and SCs, with the aim to evaluate the therapeutic potential of SCs in regenerative medicine. We showed that SCs successfully underwent osteogenic, chondrogenic and adipogenic differentiation and determined the expression profile of canonical MSC markers on the SC surface. Besides, SCs rescued T helper (Th) cells from undergoing apoptosis, promoted the anti-inflammatory phenotype of these cells, but did not regulate Th cell proliferation. MSCs impaired the Th17-mediated response; on the other hand, SCs suppressed the inflammatory polarisation in general. SCs induced M2 macrophage polarisation more effectively than MSCs. For the first time, we demonstrated here the ability of SCs to transfer mitochondria to immune cells. Our results indicate that SCs are a type of MSCs and modulate the reactivity of the immune system. Therefore, we suggest that SCs are promising candidates for application in regenerative medicine due to their anti-inflammatory and protective effects, especially in the therapies for diseases associated with testicular tissue inflammation.