Location: Diet, Genomics and Immunology LaboratoryTitle: Immune regulation of epithelial cell function: Implications for GI pathologies Author
Submitted to: International Dairy Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/15/2010
Publication Date: 3/15/2010
Citation: Shea-Donohue, T., Notari, L., Urban Jr, J.F., Zhao, A. 2010. Immune regulation of epithelial cell function: Implications for GI pathologies. International Dairy Journal. 20(4):248-252. Interpretive Summary: More than one third of the world’s population is infected with gastrointestinal roundworms (worms). In general, most gut worms induce an elevation of Th2 cytokines linked to protective immunity against worm infection. The rising prevalence of autoimmune diseases including diabetes, inflammatory bowel disease, and celiac disease, is mirrored by the decreasing incidence of worm infection and this has been attributed, in part, to Th cell responses. This relationship between the epidemiology of these diseases forms the basis for the ‘‘hygiene hypothesis’’ that links improvements in hygienic measures to an increase in autoimmune and allergic diseases. Although this concept does not address the influence of other factors such as environmental pollutants or changes in diet, it does support the importance of Th cell cytokines in intestinal health. The protective effects of worm infection were attributed to the well-documented ability of Th2 cytokines to decrease Th1 cytokine production or to promote the development of T regulatory cells. These features are studied to show how the major regulatory mechanisms in the immune system that control the balance of cytokines can affect the intestine and the normal immune balance and nutrient absorption that are characteristic of good intestinal function.
Technical Abstract: The mammalian immune system is a complex and dynamic network that recognizes, responds, and adapts to numerous foreign and self molecules. CD4+ T cells orchestrate adaptive immune responses, and upon stimulation by antigen, naive CD4+ T cells proliferate and differentiate into various T cell subsets, including T helper (Th) 1, Th2, and Th17 effector cells, and T regulatory cells (Treg). Each of the T cell subsets is characterized by distinct profiles of cytokines and carries out distinct and sometimes opposing activities. Initiated by IL-12 released from dendritic cells, the development of Th1 cells is the typical host response against the invasion of intracellular pathogens such as bacteria or viruses. Th1 cells deliver cell-mediated immunity through their secreted cytokines such as IFN-gamma, TNF-alpha, IL-1 beta, IL-2, and IL-12, and are responsible for the clearance of intracellular pathogens. Th2 cells are initiated by IL-4 and develop in response to allergens or the invasion of extracellular pathogens. Th2 cytokines include IL-4, IL-5, and IL-13, and are particularly important for allergic responses and the clearance of parasites.