scholarly journals Th17 Cells in Inflammatory Bowel Disease: Cytokines, Plasticity, and Therapies

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Junjun Zhao ◽  
Qiliang Lu ◽  
Yang Liu ◽  
Zhan Shi ◽  
Linjun Hu ◽  
...  
Keyword(s):  
Immune System ◽  
Autoimmune Diseases ◽  
Bowel Disease ◽  
T Helper Cells ◽  
Th17 Cells ◽  
Complex Disease ◽  
T Helper ◽  
Autoimmune Inflammation ◽  
Th Differentiation ◽  
Inflammatory Bowel

Autoimmune diseases (such as rheumatoid arthritis, asthma, autoimmune bowel disease) are a complex disease. Improper activation of the immune system or imbalance of immune cells can cause the immune system to transform into a proinflammatory state, leading to autoimmune pathological damage. Recent studies have shown that autoimmune diseases are closely related to CD4+ T helper cells (Th). The original CD4 T cells will differentiate into different T helper (Th) subgroups after activation. According to their cytokines, the types of Th cells are different to produce lineage-specific cytokines, which play a role in autoimmune homeostasis. When Th differentiation and its cytokines are not regulated, it will induce autoimmune inflammation. Autoimmune bowel disease (IBD) is an autoimmune disease of unknown cause. Current research shows that its pathogenesis is closely related to Th17 cells. This article reviews the role and plasticity of the upstream and downstream cytokines and signaling pathways of Th17 cells in the occurrence and development of autoimmune bowel disease and summarizes the new progress of IBD immunotherapy.

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

2020 ◽  
Vol 21 (9) ◽  
pp. 3379 ◽  
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.

scholarly journals Ustekinumab in Psoriasis Immunopathology with Emphasis on the Th17-IL23 Axis: A Primer

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Pascale Quatresooz ◽  
Trinh Hermanns-Lê ◽  
Gérald E. Piérard ◽  
Philippe Humbert ◽  
Philippe Delvenne ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Inflammatory Bowel Diseases ◽  
T Helper Cells ◽  
Th17 Cells ◽  
Human Monoclonal Antibody ◽  
Biologic Therapies ◽  
T Helper ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Th 1

Psoriasis is a chronic relapsing immunoinflammatory dermatosis that is commonly associated with systemic comorbidities. The pathogenic importance of interleukin (IL)-12 and IL-23 is beyond doubt, as well as the involvement of T helper cells (Th)1 and Th17 cells. There is upregulation of the p40 subunit shared by IL-12 and IL-23 and of the IL-23 p19 subunit, but not an increased expression of the IL-12 p35 subunit. This indicates that IL-23 appears more involved than IL-12 in the pathogenesis of psoriatic plaques. Ustekinumab is a fully human monoclonal antibody of the immunoglobulin (Ig) G1 class targeting the p40 subunit common to both IL-12 and IL-23, thus inhibiting both IL-12 and IL-23 receptor-mediated signalling. Ustekinumab is part of the recent biologic therapies active in psoriasis, autoimmune arthritides, and inflammatory bowel diseases.

Natural Products: Experimental Efficient Agents for Inflammatory Bowel Disease Therapy

2020 ◽  
Vol 25 (46) ◽  
pp. 4893-4913 ◽  
Author(s):  
Fan Cao ◽  
Jie Liu ◽  
Bing-Xian Sha ◽  
Hai-Feng Pan
Keyword(s):  
Inflammatory Bowel Disease ◽  
Natural Products ◽  
Immune System ◽  
Bowel Disease ◽  
Therapeutic Potential ◽  
Adaptive Immune System ◽  
Receptor Protein ◽  
Intestinal Epithelia ◽  
Inflammatory Bowel ◽  
The Individual

: Inflammatory bowel disease (IBD) is a chronic, elusive disorder resulting in relapsing inflammation of intestine with incompletely elucidated etiology, whose two representative forms are ulcerative colitis (UC) and Crohn’s disease (CD). Accumulating researches have revealed that the individual genetic susceptibility, environmental risk elements, intestinal microbial flora, as well as innate and adaptive immune system are implicated in the pathogenesis and development of IBD. Despite remarkable progression of IBD therapy has been achieved by chemical drugs and biological therapies such as aminosalicylates, corticosteroids, antibiotics, anti-tumor necrosis factor (TNF)-α, anti-integrin agents, etc., healing outcome still cannot be obtained, along with inevitable side effects. Consequently, a variety of researches have focused on exploring new therapies, and found that natural products (NPs) isolated from herbs or plants may serve as promising therapeutic agents for IBD through antiinflammatory, anti-oxidant, anti-fibrotic and anti-apoptotic effects, which implicates the modulation on nucleotide- binding domain (NOD) like receptor protein (NLRP) 3 inflammasome, gut microbiota, intestinal microvascular endothelial cells, intestinal epithelia, immune system, etc. In the present review, we will summarize the research development of IBD pathogenesis and current mainstream therapy, as well as the therapeutic potential and intrinsic mechanisms of NPs in IBD.

scholarly journals Neonatal lymphocyte subpopulations analysis and maternal preterm premature rupture of membranes: a pilot study

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Margherita Amadi ◽  
Silvia Visentin ◽  
Francesca Tosato ◽  
Paola Fogar ◽  
Giulia Giacomini ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
T Helper Cells ◽  
Lymphocyte Subpopulations ◽  
T Helper ◽  
Premature Rupture Of Membranes ◽  
Premature Rupture ◽  
Preterm Premature Rupture ◽  
Helper Cells

Abstract Objectives Preterm premature rupture of membranes (pPROM) causes preterm delivery, and increases maternal T-cell response against the fetus. Fetal inflammatory response prompts maturation of the newborn’s immunocompetent cells, and could be associated with unfavorable neonatal outcome. The aims were to examine the effects of pPROM (Mercer BM. Preterm premature rupture of the membranes: current approaches to evaluation and management. Obstet Gynecol Clin N Am 2005;32:411) on the newborn’s and mother’s immune system and (Test G, Levy A, Wiznitzer A, Mazor M, Holcberg G, Zlotnik A, et al. Factors affecting the latency period in patients with preterm premature rupture of membranes (pPROM). Arch Gynecol Obstet 2011;283:707–10) to assess the predictive value of immune system changes in neonatal morbidity. Methods Mother-newborn pairs (18 mothers and 23 newborns) who experienced pPROM and controls (11 mothers and 14 newborns), were enrolled. Maternal and neonatal whole blood samples underwent flow cytometry to measure lymphocyte subpopulations. Results pPROM-newborns had fewer naïve CD4 T-cells, and more memory CD4 T-cells than control newborns. The effect was the same for increasing pPROM latency times before delivery. Gestational age and birth weight influenced maturation of the newborns’ lymphocyte subpopulations and white blood cells, notably cytotoxic T-cells, regulatory T-cells, T-helper cells (absolute count), and CD4/CD8 ratio. Among morbidities, fewer naïve CD8 T-cells were found in bronchopulmonary dysplasia (BPD) (p=0.0009), and more T-helper cells in early onset sepsis (p=0.04). Conclusions pPROM prompts maturation of the newborn’s T-cell immune system secondary to antigenic stimulation, which correlates with pPROM latency. Maternal immunity to inflammatory conditions is associated with a decrease in non-major histocompatibility complex (MHC)-restricted cytotoxic cells.

scholarly journals 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

1999 ◽  
Vol 190 (5) ◽  
pp. 607-616 ◽  
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.

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

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
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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