Marine peptides as immunomodulators: Californiconus californicus-derived synthetic conotoxins induce IL-10 production by regulatory T cells (CD4(+)Foxp3(+))

Context: CD4(+) T lymphocytes are able to differentiate into distinct subtypes according to several immunological scenarios, including T helper (Th)1, Th2, Th17 and regulatory T (Treg) cells. CD4(+) T cells are phenotypically flexible and have specific ion channels, such as the nicotinic acetylcholine receptors (nAChR) that could be modulated by peptides produced by marine snails, known as conotoxins. Their effect on T lymphocytes has not been explored and emerging evidence suggests that these peptides may have immunomodulatory activities. Objective: This study investigated the effect of two Californiconus californicus-derived synthetic conotoxins on the proliferation and differentiation of T lymphocyte subpopulations Th1, Th2, Th17 and Treg. Methods: Cells from lymph nodes of BALB/c mice were cultured in the presence of conotoxins cal14.1b and cal14.2c (5.5 mu M), during 96 h. Cell proliferation and intracellular cytokine production (IFN-gamma, IL-4, IL-17 and IL-10) were analyzed by flow cytometry. Results and Discussion: cal14.1b and cal14.2c increased intracellular IL-10 production in Treg (CD3(+)CD4(+)Foxp3(+)) cells and decreased intracellular IL-17 production (CD3(+)CD4(+)) after 72 h of culture. Conotoxins did not show any effect on T cell proliferation nor Th1/Th2 balance. Conclusion: These results suggest that synthetic conotoxins exert immunomodulatory activity, especially by regulating specific functions on T lymphocytes.