Regulatory T Cells, a Viable Target Against Airway Allergic Inflammatory Responses in Asthma

Abstract

Asthma is a multifactorial disorder characterized by the airway chronic inflammation, hyper-responsiveness (AHR), remodeling, and reversible obstruction. Although asthma is known as a heterogeneous group of diseases with various clinical manifestations, recent studies suggest that more than half of the clinical cases are ‘‘T helper type 2 (Th2)-high’’ type, whose pathogenesis is driven by Th2 responses to an inhaled allergen from the environmental exposures. The intensity and duration of inflammatory responses to inhaled allergens largely depend on the balance between effector and regulatory cells, but many questions regarding the mechanisms by which the relative magnitudes of these opposing forces are remained unanswered. Regulatory T cells (Tregs), which comprise diverse subtypes with suppressive function, have long been attracted extensive attention owing to their capability to limit the development and progression of allergic diseases. In this review we seek to update the recent advances that support an essential role for Tregs in the induction of allergen tolerance and attenuation of asthma progression once allergic airway inflammation established. We also discuss the current concepts about Treg induction and Treg-expressed mediators relevant to controlling asthma, and the therapies designed based on these novel insights against asthma in clinical settings.

Thymically imprinted differential responsivity of naïve CD4 T cells to IL2 results in a heterogeneity of both Treg induction and subsequent effector functioning

“…Given the known interaction between Tregs and both monocyte/macrophages and PMN/granulocytes in the resolution of airway inflammation (Soroosh et al, 2013; Zhang et al, 2022), we hypothesized that factors secreted by the differentiated iTregs themselves might impact myeloid cell differentiation. To pursue this hypothesis, we performed in vitro bone marrow monocyte differentiation co-culture assays.…”

Ferroptosis-related genes are involved in asthma and regulate the immune microenvironment

“…Interestingly, we discovered a negative correlation between CISD1 and Tregs, pointing to the potential role of CISD1 in immune cell infiltration. Tregs were viable target against airway allergic inflammatory responses, and played an indispensable role in the maintenance of immune tolerance in asthma (Li et al, 2021;Zhang et al, 2022). By upregulating immunosuppressive molecules and suppressing genes, the Tregs fraction of CD4 + T-cell prevented the development of proinflammatory activities and reduced inflammation (Burzyn et al, 2013;van der Veeken et al, 2016).…”

Tyndallized Bacteria Preferentially Induce Human Macrophage M1 Polarization: An Effect Useful to Balance Allergic Immune Responses and to Control Infections

“…M1 macrophages, which are the prototypic pro-inflammatory macrophage subset, are induced by the exposure to interferon and/or lipopolysaccharide (LPS), while M2, with prominent anti-inflammatory and reparative functions, are induced by TH2 cytokines (IL-4 and IL-13) [ 21 ]. Antigen processing and innate immune receptor activation, which lead to higher IFN-gamma and IL-12 levels, favor TH1 polarization, while increased levels of IL-4 favor TH2 polarization and increased IL-10 levels induce Treg activities [ 27 ].…”

“…TB could also potentially affect adaptive immune response activation. It is known that IL-1β and IL-6 control proliferation, activation and apoptosis of lymphocytes [ 43 ], while TGF-β induce Treg activation [ 27 ].…”