JAK-STAT and intestinal mucosal immunology

Aaron F Heneghan, Joseph F Pierre, Kenneth A Kudsk, Aaron F Heneghan, Joseph F Pierre, Kenneth A Kudsk

Abstract

The intestinal mucosal immune system is challenged with bacteria, viruses, and parasites, in addition to food and environmental antigens, that require dynamic immune responsiveness for homeostasis. One central signaling pathway is JAK-STAT, which regulates the adaptive and innate immune arms of mucosal immunity as well as epithelial repair and regeneration. Adaptive immunity includes lymphocyte mediated secretion of specific antibodies, while innate immune respones include secretion of non-antigen specific compounds. This review examines effects of specialized nutrition support on JAK-STAT in innate immune function and in lymphocyte modulation and epithelial antibody transport in gut-associated lymphoid tissue.

Keywords: JAK-STAT; Paneth cells; Peyer patches; STAT4; STAT6; goblet cells; mucosal immunity; pIgR; sIgA.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3876429/bin/jkst-2-e25530-g1.jpg
Figure 1. Adaptive mucosal immune function in the small intestine. Naïve T and B lymphocytes enter the Peyer patches (PP) via interaction with their integrins L-selectin or α4β7 and MAdCAM-1 which is present on the high endothelial venules (HEV) of the PP. The cells are sampled and sensitized to antigen in Microfold (M) cells inside the PP. Sensitized cells return to the peripheral circulation via the thoracic duct and are distributed to other mucosal effector sites. Within these effector sites, Th2 cytokines (IL-4, IL-5, IL-6, and IL-10) produced by T lymphocytes stimulate maturation of B cells into competent IgA producing cells, i.e., plasma cells. These cells produce the principal molecule of adaptive immunity, dimeric IgA, in the lamina propria where it undergoes transepithelial transport via polymeric immunoglobulin receptor (pIgR) which is expressed on the basal surface of mucosal enterocytes.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3876429/bin/jkst-2-e25530-g2.jpg
Figure 2. JAK-STAT and T helper cell differentiation of naïve T cells. Naïve T cells differentiate into several T helper cell subsets, Th1, Th2, of Th17. IL-12 is required for the differentiation into Th1 cells that secrete IFN-γ, TNF-α, and IL-2 to generate a response to intracellular pathogens. IL-4 is required for the differentiation into Th2 cells that secrete IL-4, IL-5, and IL-10 to generate defenses against Helminth infections. IL6, IL-21, and IL-23 are required for the differentiation into Th17 cells that secrete IL-17 and IL-22 to promote defense against extracellular pathogens.

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