T-Cell Differentiation and Intestinal Mucosal Barrier Function

// Amy Doyle, MS, CNS


T-Cell Differentiation and Intestinal Mucosal Barrier Function

The intestinal barrier encounters external stimuli from the environment on a daily basis. This barrier is comprised of a cellular layer, known as the epithelium, as well as a mucosal layer that consists of a sophisticated network of glycoproteins that function to protect the underlying single-celled layer. Within this structure are the mucosal-associated lymphoid tissue (MALT) and the gut-associated lymphoid tissue (GALT), which collectively govern the interactions between both innocuous and harmful stimuli and the host, and encompass more than 70% of the immune system.1

Structural changes to the intestinal barrier disruption can compromise the composition and function of the mucosal barrier.

As the largest mucosal surface in the human body, the gastrointestinal mucosal layer can be found in the stomach, small intestine, and colon with specialized properties and composition in each. Along with being home to microflora, the mucosal layer is also the site of digestive enzyme secretion and the primary site of nutrient absorption. As the body’s first line of defense against foreign antigens, it is heavily populated with various lymphocytes, antimicrobial peptides, macrophages and natural killer (NK) cells, and serves as the origin for secretory immunoglobulin A (sIgA) production.

Foreign antigens that reach the gastrointestinal tract are initially confronted by macrophages within the mucosal barrier. These macrophages, usually dendritic cells (DCs), present the antigens to CD4+ T helper lymphocytes which then differentiate into T helper cell subsets, including Th1, Th2, and Th17.2 This process known as transcription, is driven by genetic susceptibility, the type of antigen presented, and types of cytokines produced by the encounter.2 What follows is a discussion of the immune response within the mucosal layer and its influence on T-cell differentiation.

Th1 Differentiation

Th1 differentiation is directed largely by IL-12 and IFN-gamma and follows microbial stimulation of DCs and NK cells.3 As part of the innate immune response, Th1 cells further recruit macrophages and promote phagocytosis. Production of IL-12 and IFN- gamma continues, which serves to inhibit differentiation toward a Th2 or Th17 response. These Th1 mediated cytokines activate adaptive immunity, an IgG response, and further polarize the immune response to favor Th1 cell differentiation, a process known as amplification.3

Th2 Differentiation

Differentiation toward a Th2 response is triggered mainly by IL-4, a cytokine also associated with IgE. Th2 cells also secrete IL-4 and other cytokines including IL-10, IL-5, IL-6, IL-9, and IL-13 which are responsible for eosinophil, B cell, and mast cell activation.3 These cytokines also induce peristalsis in the gut and increase mucus secretion.

Th17 Differentiation

Polarization toward Th17 production is driven by bacteria and fungi and IL-6, IL-1, and IL-23.4 Th17 cells recruit neutrophils and a variety of macrophages along with producing IL-17 and IL-23.4

Mucosal Barrier and Overall Health

It is important to recognize the interaction between the gut microflora, immune system, and the epithelial lining, and the influence of these factors on the mucosal barrier.5 Structural changes to the intestinal barrier like microbiome, epithelial, or tight junction disruption can compromise the composition and function of the mucosal barrier.5 This can lead to a risk of increased permeability and an accompanying risk of gastrointestinal and extra-intestinal sequelae. Atrophy of the mucosal barrier can result in translocation of bacteria and other macromolecules from the environment across the epithelial barrier and provoke aberrant T cell differentiation and immune response.2 These interactions along with assessing the patient’s stress, diet, and age-related digestive changes may indicate a need for targeted support for proper gastrointestinal function and defense.

Gastrointestinal Restoration Program

Amy Doyle, MS, CNS

Amy Doyle is a board certified nutrition specialist and owner of White Stone Wellness. She graduated from the New York Chiropractic College with her Master’s degree in Applied Clinical Nutrition. She is a member of the American College of Nutrition and American Nutrition Association. She currently has a private practice at Willow Health and Wellness Center in Baldwinsville, NY. Amy helps people with gastrointestinal health, food sensitivities, and metabolic health. Her approach considers the effect of the body on the mind as well as the mind on the body. She is also passionate about the crusade for schools to feed our children healthy, whole foods and is an advocate for establishing community gardens in areas of need.

  1. Vighi G, Marcucci F, Sensi L, et al. Allergy and the gastrointestinal system. Clin Exp Immunol. 2008. 152 (Suppl. 1):3-6.
  2. Fasano A, Shea-Donohue T. Mechanisms of Disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol.. September 2005. 2(9):416-22.
  3. Sult T. Th1/Th2 Balance: A Natural Therapeutic Approach to Th2 Polarization in ... ANSR. 2003.
  4. Omenetti S, Pizarro S. The Treg/Th17 Axis: A Dynamic Balance Regulated by the Gut Microbiome. Front Immunol. December 2015. 6:639.
  5. De Santis S, Cavalcanti E, Mastronardi M, et al. Nutritional Keys for Intestinal Barrier Modulation. Front Immunol. December 2016. 6:612.

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