This week, we learn more about how mesenchymal stem cells affect the immune system, why CX3CR1 is needed to clear a yeast infection and how the body stops helminths in their tracks.
Stem Cells and Immunosuppression
A recent study on mesenchymal stem cell (MSC) therapy has uncovered a novel mechanism of immunosuppression in the colon. The French group was using MSC therapy to counter gastrointestinal complications caused during tumor radiotherapy. They found that the treatment reduced colon epithelial damage, but also reduced the relative proportion of infiltrating CD4+ and CD8+ T cells. There was also a marked reduction of T cell activation and proliferation. This downregulation was parallel with significant increases of corticosterone secretion and subsequent interleukin-10 expression. Experiments with a glucocorticoid receptor blocker pointed towards an impaired TCR signal transduction initiated by the MSC treatment. It will be interesting to see if this finding can help improve MSC treatment of inflammatory bowel disease (IBD).
CX3CR1 and Candida
Crohn’s disease (CD) is often associated with harmful Candida albicans infections. Unlocking the secrets behind how the body controls Candida infections could be beneficial for CD patients. In this study, performed by the NIH, it was determined that the chemokine receptor CX3CR1 is crucial for macrophage survival in the kidney, the preferred hideout for Candida. During an infection, it was found that CX3CR1 was upregulated in the kidney macrophages. Mice deficient in CX3CR1 had a high mortality and were found to have uncontrolled Candida growth in the kidneys. The loss of the receptor prevented macrophages from accumulating in the kidney and engulfing the yeast. Given the growing role CX3CR1 in the pathogenesis of IBD, it will be interesting to consider if this receptor forms a link between CD and associated Candidiasis.
Helminth Induced Immune Reactions
As intestinal worms are becoming a new therapeutic for IBD, it’s interesting to learn about the immune responses that are induced upon their introduction to the body. A Japanese study in the Journal of Experimental Medicine has now shown that the skin does its best to prevent reinfection of Nippostrongylus brasiliensis. This species is similar to Necator americanus, which is used in IBD therapy. These worms enter through the skin. The scientists found that during the first exposure the skin had a limited response. However during a second application, there was a huge immune reaction, which was characterized by cellular infiltrates that trapped the larvae. The key immune cell mediating this trapping was the basophil, which detected worm antigens (bound to antibodies) using FcεRI and elicited the help of macrophages. It will be useful to determine if this process hinders worm treatment in IBD patients who have already had helminth infections.
- Bessout, R., mont, A. S. E., Demarquay, C., Charcosset, A., Benderitter, M., & Mathieu, N. (2013). Mesenchymal stem cell therapy induces glucocorticoid synthesis in colonic mucosa and suppresses radiation-activated T cells: new insights into MSC immunomodulation, Mucosal Immunology. 1–14. doi:10.1038/mi.2013.85
- Lionakis, M. S., Swamydas, M., Fischer, B. G., Plantinga, T. S., Johnson, M. D., Jaeger, M., et al. (2013). CX3CR1-dependent renal macrophage survival promotes Candida control and host survival. The Journal of clinical investigation. doi:10.1172/JCI71307DS1
- Obata-Ninomiya, K., Ishiwata, K., Tsutsui, H., Nei, Y., Yoshikawa, S., Kawano, Y., et al. (2013). The skin is an important bulwark of acquired immunity against intestinal helminths. The Journal of experimental medicine, 18(4), 1. do