Sa1780 Comprehensive T Helper Cell Profiling Reveals Concomitant Upregulation of Regulatory T Cells and TH17 Cells in Active Inflammatory Bowel Disease

This review summarizes the current scientific evidence on the role of different T helper (Th) cell subsets, key cytokines, and chemokines in inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. According to modern concepts, not only type Th1, but also Th17, cytokines, and other cells of innate and adaptive immunity are involved in the immunopathogenesis of IBD. Most of the review is devoted to the current understanding of the role of polarized Th17 cells and subpopulations of follicular Th cells, the main function of which is to form a specific humoral immune response in IBD mediated by B cells. The role of the intestinal microbiota in the Th cell polarization, that is, their differentiation, accompanied by the acquisition of characteristics inherent in a particular subpopulation is discussed. The presented data are important for understanding the role of immune processes, including microbiome-associated ones, in the pathogenesis of IBD. Key words: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, T helper cell subsets, cytokines, chemokines, gut microbiome

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Interplay between Cytokine Circuitry and Transcriptional Regulation Shaping Helper T Cell Pathogenicity and Plasticity in Inflammatory Bowel Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21093379 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3379 ◽

Cited By ~ 2

Author(s):

Shin-Huei Fu ◽

Ming-Wei Chien ◽

Chao-Yuan Hsu ◽

Yu-Wen Liu ◽

Huey-Kang Sytwu

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

T Helper Cells ◽

Intestinal Inflammation ◽

T Helper Cell ◽

Helper Cell ◽

T Helper ◽

Local Immunity ◽

Helper Cells ◽

Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic disorder manifested as Crohn’s disease (CD) and ulcerative colitis (UC) characterized by intestinal inflammation and involves a dysregulated immune response against commensal microbiota through the activation of CD4 T helper cells. T helper cell differentiation to effector or regulatory phenotypes is controlled by cytokine networks and transcriptional regulators. Distinct polarized T helper cells are able to alter their phenotypes to adapt to diverse and fluctuating physiological environments. T helper cells exhibit intrinsic instability and flexibility to express cytokines of other lineages or transdifferentiate from one T helper cell type to another in response to various perturbations from physiological cytokine milieu as a means of promoting local immunity in response to injury or ensure tissue homeostasis. Furthermore, functional plasticity and diversity of T helper cells are associated with pathogenicity and are critical for immune homeostasis and prevention of autoimmunity. In this review, we provide deeper insights into the combinatorial extrinsic and intrinsic signals that control plasticity and transdifferentiation of T helper cells and also highlight the potential of exploiting the genetic reprogramming plasticity of T helper cells in the treatment of IBD.

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Alteration of Interleukin 4 Production Results in the Inhibition of T Helper Type 2 Cell–Dominated Inflammatory Bowel Disease in T Cell Receptor α Chain–Deficient Mice

Journal of Experimental Medicine ◽

10.1084/jem.190.5.607 ◽

1999 ◽

Vol 190 (5) ◽

pp. 607-616 ◽

Cited By ~ 75

Author(s):

Hideki Iijima ◽

Ichiro Takahashi ◽

Daisuke Kishi ◽

Jin-Kyung Kim ◽

Sunao Kawano ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

T Cell ◽

T Cell Receptor ◽

Bowel Disease ◽

Cell Receptor ◽

Interleukin 4 ◽

T Helper ◽

Inflammatory Bowel ◽

Α Chain

T cell receptor α chain–deficient (TCR-α−/−) mice are known to spontaneously develop inflammatory bowel disease (IBD). The colitis that develops in these mice is associated with increased numbers of T helper cell (Th)2-type CD4+TCR-ββ (CD4+ββ) T cells producing predominantly interleukin (IL)-4. To investigate the role of these Th2-type CD4+ββ T cells, we treated TCR-α−/− mice with anti–IL-4 monoclonal antibody (mAb). Approximately 60% of TCR-α−/− mice, including those treated with mock Ab and those left untreated, spontaneously developed IBD. However, anti–IL-4 mAb–treated mice exhibited no clinical or histological signs of IBD, and their levels of mucosal and systemic Ab responses were lower than those of mock Ab–treated mice. Although TCR-α−/− mice treated with either specific or mock Ab developed CD4+ββ T cells, only those treated with anti–IL-4 mAb showed a decrease in Th2-type cytokine production at the level of mRNA and protein and an increase in interferon γ–specific expression. These findings suggest that IL-4–producing Th2-type CD4+ββ T cells play a major immunopathological role in the induction of IBD in TCR-α−/− mice, a role that anti–IL-4 mAb inhibits by causing Th2-type CD4+ββ T cells to shift to the Th1 type.

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Generation of IL-8 and IL-9 Producing CD4+T Cells Is Affected by Th17 Polarizing Conditions and AHR Ligands

Mediators of Inflammation ◽

10.1155/2014/182549 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 13

Author(s):

Michaela Gasch ◽

Tina Goroll ◽

Mario Bauer ◽

Denise Hinz ◽

Nicole Schütze ◽

...

Keyword(s):

T Cells ◽

T Helper Cells ◽

Th17 Cells ◽

Immune Cell ◽

T Helper Cell ◽

Helper Cell ◽

T Helper ◽

Helper Cells ◽

Aryl Hydrocarbon

The T helper cell subsets Th1, Th2, Th17, and Treg play an important role in immune cell homeostasis, in host defense, and in immunological disorders. Recently, much attention has been paid to Th17 cells which seem to play an important role in the early phase of the adoptive immune response and autoimmune disease. When generating Th17 cells underin vitroconditions the amount of IL-17A producing cells hardly exceeds 20% while the nature of the remaining T cells is poorly characterized. As engagement of the aryl hydrocarbon receptor (AHR) has also been postulated to modulate the differentiation of T helper cells into Th17 cells with regard to the IL-17A expression we ask how far do Th17 polarizing conditions in combination with ligand induced AHR activation have an effect on the production of other T helper cell cytokines. We found that a high proportion of T helper cells cultured under Th17 polarizing conditions are IL-8 and IL-9 single producing cells and that AHR activation results in an upregulation of IL-8 and a downregulation of IL-9 production. Thus, we have identified IL-8 and IL-9 producing T helper cells which are subject to regulation by the engagement of the AHR.

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