The axis IL-10/claudin-10 is implicated in the modulation of aggressiveness of melanoma cells by B-1 lymphocytes.

B-1 lymphocytes are known to increase the metastatic potential of B16F10 melanoma cells via the extracellular signal-regulated kinase (ERK) pathway. Since IL-10 is associated with B-1 cells performance, we hypothesized that IL-10 could be implicated in the progression of melanoma. In the present work, we found that the C57BL/6 mice, inoculated with B16F10 cells that were co-cultivated with B-1 lymphocytes from IL-10 knockout mice, developed fewer metastatic nodules than the ones which were injected with the melanoma cells that were cultivated in the presence of wild-type B-1 cells. The impairment of metastatic potential of the B16F10 cells was correlated with low activation of the ERK signaling pathway, supporting the idea that the production of IL-10 by B-1 cells influences the behavior of the tumor. A microarray analysis of the B-1 lymphocytes revealed that IL-10 deficiency is associated with down-regulation of the genes that code for claudin-10, a protein that is involved in cell-to-cell contact and that has been linked to lung adenocarcinoma. In order to determine the impact of claudin-10 in the cross-talk between B-1 lymphocytes and the B16F10 tumor cells, we took advantage of small interfering RNA. The silencing of claudin-10 gene in B-1 lymphocytes inhibited activation of the ERK pathway and abrogated the B-1-induced aggressive behavior of the B16F10 cells. Thus, our findings suggest that the axis IL-10/claudin-10 is a promising target for the development of therapeutic agents against aggressive melanoma.

Evaluation of Experimental Infection with L. ( L.) Amazonensis in X-Linked Immunodeficient Mice.

B-1 cells are a subtype of B cells with peculiar characteristics. These cells are distinct from B-2 lymphocytes in their morphology, ontogeny, tissue distribution, and phenotypic functional features. B-1 cells can participate in the immune response in several ways, for example, by being recruited to inflammatory foci, producing large amounts of IL-10 cytokine, and differentiating into IgM-secreting cells or phagocytes. Nevertheless, the role of B-1 cells in the pathogenesis of experimental leishmaniasis has not been fully elucidated. Here we evaluated the role of B-1 cells in Leishmania ( L.) amazonensis infection using X-linked immunodeficient (XID) mice that possess a mutation in Bruton's tyrosine kinase (Btk) that leads to a reduced number of B-1 cells. The course of infection and the corresponding immune response were analyzed in infected mice. XID mice showed an increase in parasite number in paws, lymph nodes, and spleen compared to BALB/c infected controls. Infected XID mice had higher IL-10 levels and lower anti- Leishmania IgM. The adoptive transfer of peritoneal B-1 cells into XID mice restored peritoneal B-1 cells and parasite burden in the footpad in a pattern similar to that observed in the BALB/c controls at 10 wk. Our results demonstrate the higher susceptibility of XID mice to infection with L. ( L.) amazonensis compared to controls. In addition, we show that the presence of B-1 cells contributes to improved animal resistance to parasites, suggesting that these cells are involved in the control of cutaneous infection caused by L. ( L.) amazonensis.

B-1 cells contribute to susceptibility in experimental infection with Leishmania (Leishmania) chagasi.

The immune response to leishmaniasis is complex, and the result of infection depends on both the genetic composition of the Leishmania species and the immunity of the host. Clinical and experimental evidence suggest that the activation of B cells leads to exacerbation of visceral leishmaniasis. However, the role of B-1 cells (a subtype of B lymphocytes) in the pathogenesis of experimental visceral leishmaniasis has not yet been elucidated. In this study, we investigated the importance of B-1 cells in experimental infection with Leishmania. (L.) chagasi. Our results showed that BALB/XID mice (X-linked immunodeficient mice which are genetically deficient in B-1 cells) infected with L. (L.) chagasi for 45 days had a significant reduction in parasite load in the spleen when compared with control mice. Cytokine analysis showed that the BALB/XID mice had lower amounts of IL-10 in their sera compared with control group. In addition, the transfer of B-1 cells from wild type mice into IL-10KO animals led to an increase in susceptibility to L. (L.) chagasi infection in the IL-10KO mice, suggesting that the IL-10 produced by these cells is important in experimental infection. Our results suggest that B-1 cells may play an important role in susceptibility to L. (L.) chagasi.