The Mechanisms of Effector Th Cell Responses Contribute to Treg Cell Function: New Insights into Pathogenesis and Therapy of Asthma

Abstract

CD4 + helper T (Th) cell subsets are critically involved in the pathogenesis of asthma. Naive Th cells differentiate into different subsets under the stimulation of different sets of cytokines, and the differentiation process is dominantly driven by lineage specific transcription factors, such as T-bet (Th1), GATA3 (Th2), RORγt (Th17) and Foxp3 (Treg). The differentiation mechanisms driven by these transcription factors are mutually exclusive, resulting in functional inhibition of these Th subsets to each other, particularly prominent between effector Th cells and Treg cells, such as Th2 versus Treg cells and Th17 versus Treg cells. Being of significance in maintaining immune homeostasis, the balance between effector Th cell response and Treg cell immunosuppression provides an immunological theoretical basis for us to understand the immunopathological mechanism and develop the therapy strategies of asthma. However, recent studies have found that certain factors involved in effector Th cells response, such as cytokines and master transcription factors (IL-12 and T-bet of Th1, IL-4 and GATA3 of Th2, IL-6 and RORγt of Th17), not only contribute to immune response of effector Th cells, but also promote the development and function of Treg cells, therefore bridging the interplay between effector Th cell immune responses and Treg cell immunosuppression. Although we have an abundant knowledge concerning the role of these cytokines and transcription factors in effector Th cell responses, our understanding on their role in Treg cell development and function is scattered thus need to be summarized. This review summarized the role of these cytokines and transcription factors involved in effector Th cell responses in the development and function of Treg cells, in the hope of providing new insights of understanding the immunopathological mechanism and seeking potential therapy strategies of asthma.

Causal relationship between asthma and inflammatory bowel disease : A two-sample bidirectional mendelian randomization analysis

“…M1-like polarization of macrophages produces large amounts of pro-in ammatory cytokines that affect the balance of the immune system and further trigger a chronic in ammatory response, the mechanism that has been identi ed in both IBD and asthma [28,29]. Meanwhile, Treg cells, a subset of suppressive T cells, play an important role in preventing excessive immune responses, inducing immune tolerance, and preventing and controlling the development of autoimmunity [30,31]; when Treg cells decline in number or become dysfunctional, this can lead to disruption of immune homeostasis and consequently cause autoimmune diseases such as asthma and IBD [32,33].…”

Copaiba oil minimizes inflammation and promotes parenchyma re-epithelization in acute allergic asthma model induced by ovalbumin in BALB/c mice

“…This process enhances the production of FOXP3, promoting differentiation in favor of Treg cells ( Peine et al, 2016 ; Griesenauer and Paczesny, 2017 ). Additionally, the regulation of the CCR8 GATA3 receptor facilitates the migration of Tregs to the inflammatory site, thereby promoting asthma control ( Chen W. et al, 2022 ). We have confirmed that OVA-exposed animals exhibited a significant increase in positive staining for FOXP3 compared to the CONTROL group ( p < 0.05).…”

Gene Signature of Regulatory T Cells Isolated from Children with Selective IgA Deficiency and Common Variable Immunodeficiency

“…T regs isolated from CVID patients, when compared to T regs from healthy controls, were enriched in Th response-associated genes, including T cell receptor signaling pathways, and associated with Th17 cell differentiation. T reg cells were shown to regulate all types of Th response, including Th1, Th2, and Th17, and the mutual association of Th and T reg cells currently seems far more complex than the primary concept of effector Th cells and T reg cells inhibiting each other [ 62 , 63 ]. It is thus possible that impaired Ig production in CVID patients is associated with dysregulated Th response control by their T reg cells.…”