Human Fallopian Tube - Derived Mesenchymal Stem Cells Inhibit Experimental Autoimmune Encephalomyelitis by Suppressing Th1/Th17 Activation and Migration to Central Nervous System.

Mesenchymal stem cells comprise a natural reservoir of undifferentiated cells within adult tissues. Given their self-renewal, multipotency, regenerative potential and immunomodulatory properties, MSCs have been reported as a promising cell therapy for the treatment of different diseases, including neurodegenerative and autoimmune diseases. In this study, we investigated the immunomodulatory properties of human tubal mesenchymal stem cells (htMSCs) using the EAE model. htMSCs were able to suppress dendritic cells activation downregulating antigen presentation-related molecules, such as MHCII, CD80 and CD86, while impairing IFN-γ and IL-17 and increasing IL-10 and IL-4 secretion. It further correlated with milder disease scores when compared to the control group due to fewer leukocytes infiltrating the CNS, specially Th1 and Th17 lymphocytes, associated with increased IL-10 secreting Tr1 cells. Conversely, microglia were less activated and infiltrating mononuclear cells secreted higher levels of IL-4 and IL-10 and expressed reduced chemokine receptors as CCR4, CCR6 and CCR8. qPCR of the spinal cords revealed upregulation of indoleamine-2,3-dioxygenase (IDO) and brain derived neurotrophic factor (BDNF). Taken together, here evidenced the potential of htMSCs as an alternative for the treatment of inflammatory, autoimmune or neurodegenerative diseases.

Preconceptional allergen immunization can induce offspring IL-17 secreting B cells (B17): do they share similarities with regulatory B10 cells?

BACKGROUND: IL-17-producing B cells can be identified in both mice and human and were named B17 cells. The role of B17 cells still needs to be elucidated and its inflammatory or regulatory functions remain controversial. OBJECTIVE: We evaluate the effect of maternal immunization with OVA on offspring B cells that produces IL-17 and can show a regulatory potential by IL-10 production. METHODS: C57BL/6 WT, IL-10-/- or CD28-/- female mice were immunized or not with OVA in Alum, and immunized females were boosted after 10 and 20 days. Immunized and non-immunized females were mated, and pups from both groups were evaluated at 3 or 20 days old (d.o.). Some offspring from the aforementioned two groups were immunized with OVA at 3 d.o., boosted after 10 days and evaluated at 20 d.o. RESULTS: Maternal immunization with OVA induced offspring B cells to produce IL-17 at higher intensity compared to the control group of offspring at 3 d.o. This effect was maintained until 20 d.o. and even after neonatal immunization with OVA. The co-production of IL-10 on offspring IL-17+B cells is up-regulated in response to maternal immunization with OVA. Maternal immunization with OVA on IL-10-/- mice reveals reduced percentage and mean of fluorescence intensity of IL-17 on B cells of offspring. CONCLUSION: Preconception OVA immunization can induce offspring B cells that produce IL-17 at higher intensity and co-produce mainly IL-10. This could be the reason why B17 cells had been described in the literature with controversial roles upon their regulatory function.