Abstract
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.
Highlights
Since micro-environmental cytokines are critical for regulation of plasticity between T helper (Th) lineages to reprogram their differentiated states [74], it was demonstrated that Th17 cells could be converted into either regulatory T cells in the presence of transforming growth factor (TGF)-β or Th1 cells in response to inflammatory cytokine stimulation (e.g., IL-12 and IL-23) [75]
The colitogenic potential of IFN-γ-producing Th17 was verified by a study focusing on IFN-γ-deficient Th17 cells, which retained an IL-17A+ phenotype and were unable to induce colitis in a Th17-transfer colitis model, while development of disease required the transition of Th17 precursors to Th1-like cells depending on the expression of both STAT4 and T-bet [158]
The plasticity and transdifferentiation among CD4+ T cell lineages in the gut is strongly associated with Inflammatory bowel disease (IBD) pathogenicity and controlled by genetic regulation of gene expression through the concerted action of cytokines, transcription factors, and epigenetic regulators
Summary
Inflammatory bowel disease (IBD) is caused by the interplay of genetic susceptibility, environmental factors, and uncontrolled immune responses [1]. Crohn’s disease (CD) and ulcerative colitis (UC) are two major forms of IBD and present inflammatory profiles associated with complex etiopathogenic factors, including dysfunction of the intestinal immune system and disruption of intestinal epithelial barrier integrity [2]. Following the first report of association of NOD2 gene variants in CD [4], genome-wide association studies identified 242 associated genomic loci containing susceptibility genes for CD, UC, or both [5,6], providing insights into their pathogenic mechanisms Among these single nucleotide polymorphisms, an exceptional proportion of these exhibited pathophysiologically relevant associations, with mutations implicated in T cell response, T cell activation, and immunosuppression [5]. TTuGmFo-rβnseeccrroestiisofnacdtoiffr-er(TenNtFia-tαe) nisaaïvkeeyT icneflalsmimntaotoTrhy1m7.edTiuamtororprnoedcurocseids bfaycitmorm- u(TnNe cFe-lαls) aisnda lkeeayds to aicncflelaemramteadtoirnyflmamedmiatoiornp.roTdhuercaepdiebsy timarmgeutinnegcethlles ainidtialetaiodns taonadccperloergarteesdsiionnflapmhamsaetsioonf. dTihsearaspeieasre indictartgedetingbtluhe.initiation and progression phases of disease are indicated in blue
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
