The Role of T-Cell Subsets in Chronic Inflammation in Celiac Disease and Inflammatory Bowel Disease Patients: More Common Mechanisms or More Differences?

Abstract

Background: Chronic intestinal inflammation due to noninfectious causes represents a growing health issue all over the world. Celiac disease as well as inflammatory bowel diseases (IBD) like Crohn's disease and ulcerative and microscopic colitis involve uncontrolled T-cell activation and T-cell-mediated damage as common denominators. Therefore, diagnosis and treatment decisions clearly benefit from the knowledge of the intricacies of the systemic and the local T-cell activity. Summary: Depending on the cytokine milieu, CD4⁺ T cells can differentiate into proinflammatory T helper 1 (Th1), anti-inflammatory Th2, antimicrobial Th17, pleiotropic Th9, tissue-instructing Th22 cells, and in the regulatory compartment forkhead box protein 3⁺ Treg, suppressive Tr1 or Th3 cells. Additionally, follicular Th cells provide B-cell help in antibody class switching; cytotoxic CD8⁺ T cells target virus-infected or tumor cells. This review discusses our current knowledge on the contribution of defined T-cell subpopulations to establishing and maintaining chronic intestinal inflammation in either of the above entities. It also puts emphasis on the differences in the prevalence of these diseases between Eastern and Western countries. Key Messages: In celiac disease, the driving role of T cells in the lamina propria and in the epithelium mainly specific for two defined antigens is well established. Differences in genetics and lifestyle between Western and Eastern countries were instrumental in understanding underlying mechanisms. In IBD, the vast amount of potential antigens and the corresponding antigen-specific T cells makes it unlikely to find universal triggers. Increased mucosal CD4⁺ regulatory T cells in all four entities fail to control or abrogate local inflammatory processes. Thus, prevailing differences in the functional T-cell subtypes driving chronic intestinal inflammation in celiac disease and IBD at best allow some overlap in the treatment options for either disease.

T Cell-Specific Knockout of STAT3 Ameliorates Dextran Sulfate Sodium-Induced Colitis by Reducing the Inflammatory Response

“…The mucosal immune system is composed of various immune cells required for physiological immune tolerance ( 3 4 ). Aberrant infiltration of T lymphocytes is one of the main immune responses in intestinal inflammation ( 5 ). T helper (Th) 1, Th2, and Th17 cells play an important role in activating other immune cells by releasing T cell cytokines, whereas regulatory T cells are essential for restricting the expansion and overactivity of Th cells ( 6 7 ).…”

6,7,4′-Trihydroxyflavanone Protects against Dextran Sulfate Sodium-Induced Colitis by Regulating the Activity of T Cells and Colon Cells In Vivo

“…T cell differentiation into effector cells, including Th1/Th17, is a key event in colitis [ 12 , 13 , 14 ]. To differentiate these into effector cells, naïve T cells are primed by antigen-presenting cells capturing specific antigens.…”

Immunomodulatory and Antioxidant Properties of Wheat Gluten Protein Hydrolysates in Human Peripheral Blood Mononuclear Cells

“…WGPHs not only reduced PBMCs proliferation but also decreased the production of IFN-γ and IL-17 cytokines, two key mediators involved in many inflammatory conditions, such as obesity, diabetes, inflammatory bowel disease and CD [ 18 , 19 ]. Remarkably, although WGPHs had no effect on IL-4 production, a typical Th2 cytokine implicated in counteracting Th1 pathological response [ 18 ], and even decreased IL-10 production in PHA-stimulated PBMCs, WGPHs significantly increased the molar ratios of Th2/Th1 and Th2/Th17 cytokines skewing the anti-/pro-inflammatory responses toward an anti-inflammatory microenvironment.…”

“…Although inflammation is a physiological reaction, the exacerbated cytokine-mediated response can trigger several pathological conditions. Thus, an increase of pro-inflammatory Type 1 T helper (Th1) and/or Th17 cytokines, such as interferon-γ (IFN-γ) and interleukin (IL)-17, respectively, is involved in the generation of several inflammatory diseases, such as the inflammatory bowel disease and CD [ 18 , 19 ]. On the contrary, Th2 anti-inflammatory cytokines, including IL-10 and IL-4, are implicated in the control of pro-inflammatory responses [ 18 , 20 ].…”