Abstract
Infection with helminth parasites has been explored as a treatment for autoimmune and inflammatory diseases. As helminth antigens have potent immunomodulation properties capable of inducing regulatory programs in a variety of cell types, transferring cells treated with helminth antigens represents a novel extension to helminth therapy. Previous work determined that transfer of bone marrow-derived dendritic cells (DC) pulsed with a crude extract of the tapeworm Hymenolepis diminuta (HD) can suppress colitis in recipient mice. The present study explored the mechanism of disease suppression and the importance of interleukin (IL)-4 signaling. Transfer of HD-DCs suppressed dinitrobenzene sulfonic acid (DNBS)-induced colitis through activation of recipient IL-4 receptor-α. The transferred HD-DCs required IL-4Rα and the capacity to secrete IL-10 to drive IL-4 and IL-10 production and to suppress colitis in recipient mice. Treatment of DCs with IL-4 evokes an alternatively activated phenotype, but adoptive transfer of these cells did not affect the outcome of colitis. Collectively, these studies demonstrate the complexity between IL-4 and IL-10 in donor cells and recipient, and the requirement for parasite- and host-derived factors in this novel form of cell therapy. Thus IL-4Rα signaling is revealed as a pathway that could be exploited for helminth antigen cell-based therapy.
Highlights
IntroductionIn the present study, using IL-4 receptor-αknock-out mice as donors or recipients of H. diminuta (HD)-dendritic cells (DC) revealed that the anti-colitic effect of these cells required IL-4Rαon both the transferred cell and in the recipient mice
Adoptive transfer of H. diminuta (HD)-dendritic cells (DC) attenuates the severity of dinitrobenzene sulfonic acid (DNBS)-induced colitis and this is accompanied by increased production of IL-4 by mitogen-stimulated splenocytes from the recipient mice[20]
Adoptive transfer of HD-DCs suppresses DNBS-induced colitis, with the greatest benefit occurring in those mice showing significant increases in IL-10 and IL-4 production by splenic T cells[20]
Summary
In the present study, using IL-4 receptor-αknock-out mice as donors or recipients of HD-DCs revealed that the anti-colitic effect of these cells required IL-4Rαon both the transferred cell and in the recipient mice. Adoptive transfer of IL-4-induced AADC had no impact on the outcome of DNBS-induced colitis. The combination of exposure to an extract of H. diminuta and IL-4 generates a regulatory DC that can suppress colitis. These findings demonstrate the importance of IL-4Rαsignaling in helminth antigen-pulsed DCs, and highlight a novel pathway that could be exploited for the use of helminth-antigen cell-based therapy
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