Schisandrin B promotes Foxp3+ regulatory T cell expansion by activating heme oxygenase-1 in dendritic cells and exhibits immunomodulatory effects in Th2-mediated allergic asthma

Chiang, Chifa; Chang, Jer‐Hwa; Chuang, Hsiao-Chi; Fan, Chia Kwung; Hou, Tsung-Yun; Lin, Ching Yu; Lee, Yueh-Lun

doi:10.1016/j.ejphar.2022.174775

Cited by 11 publications

(6 citation statements)

References 49 publications

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“…Next, we sought to assess the polarization of virus-specific CD4 + T cells co-cultured with HO-1-expressing and HSV-infected DCs to better characterize their phenotypes. Because HO-1 expression in DCs mostly relates to Tregs [ 45 , 46 , 47 ], we assessed Forkhead box protein P3 (FoxP3) in CD4 + T cells in the co-cultures ( Figure 3 ). Interestingly, we found that virus-specific CD4 + T cells co-cultured with HSV-infected DCs previously treated with Dox ( Figure 3 I) or CoPP ( Figure 3 M) significantly expressed FoxP3 compared to the control DCs.…”

Section: Resultsmentioning

confidence: 99%

“…Among others, this molecule has been reported to act as a signaling determinant that affects DC endosomal maturation and antigen presentation by uncoupling energy production that is dependent on the mitochondria [ 51 ]. Furthermore, other CO-mediated effects include a predisposition for smaller peptides being processed and loaded onto MHC molecules [ 61 , 62 ], and cellular energetic restrictions that promote co-inhibitory molecule expression [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

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Heme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection

et al. 2023

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Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections are highly prevalent in the human population and produce mild to life-threatening diseases. These viruses interfere with the function and viability of dendritic cells (DCs), which are professional antigen-presenting cells that initiate and regulate the host’s antiviral immune responses. Heme oxygenase-1 (HO-1) is an inducible host enzyme with reported antiviral activity against HSVs in epithelial cells and neurons. Here, we sought to assess whether HO-1 modulates the function and viability of DCs upon infection with HSV-1 or HSV-2. We found that the stimulation of HO-1 expression in HSV-inoculated DCs significantly recovered the viability of these cells and hampered viral egress. Furthermore, HSV-infected DCs stimulated to express HO-1 promoted the expression of anti-inflammatory molecules, such as PDL-1 and IL-10, and the activation of virus-specific CD4+ T cells with regulatory (Treg), Th17 and Treg/Th17 phenotypes. Moreover, HSV-infected DCs stimulated to express HO-1 and then transferred into mice, promoted the activation of virus-specific T cells and improved the outcome of HSV-1 skin infection. These findings suggest that stimulation of HO-1 expression in DCs limits the deleterious effects of HSVs over these cells and induces a favorable virus-specific immune response in the skin against HSV-1.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection

et al. 2023

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“…Multiple studies have shown a balance between Treg cells and Th17 cells that regulates tolerance in the lung [50,51]. Recently, there have been multiple studies showing that different compounds have the ability to reduce different hallmarks of asthma by shifting the balance of Treg/Th17 cells towards more Treg cells in the lungs [50,[52][53][54]. A major factor disturbing this balance is particulate matter (PM), which act to amplify the Th2/ Th17 cell responses and reduce Treg cell numbers [55,56].…”

Section: Role Of Treg Cells In Asthmamentioning

confidence: 99%

Regulatory T-cells in asthma

Harb¹,

Chatila

2023

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewThis review addresses recent progress in our understanding of the role of regulatory T (Treg) cells in enforcing immune tolerance and tissue homeostasis in the lung at steady state and in directing the immune response in asthmatic lung inflammation. Recent findingsRegulatory T cells regulate the innate and adaptive immune responses at steady state to enforce immune tolerance in lung tissues at steady state and their control of the allergic inflammatory responses induced by allergens. This regulatory function can break down in the context of chronic asthmatic airway inflammation such that the lung tissue Treg cells become skewed towards a pathogenic phenotype that aggravates and perpetuates disease. Subversion of lung tissue Treg cell function involves their upregulation of Notch4 expression, which in turn acts to amplify T helper type 2 and type 17 and innate lymphoid cell type 2 responses in the airways. SummaryA dual role for Treg cells has emerged both as immune regulators but also a potential disease effectors in asthma, with implications for disease therapy.

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“…Similarly, adoptive transfer of ovalbumin (OVA) peptide-specific CD4 + CD25 + Tregs into the OVA-sensitized mice attenuated airway hyper-responsiveness (AHR) along with reduced number of eosinophils and production of Th2 cytokines in the lung following allergen challenge (5). Foxp3 + Tregs also suppress chronic allergic inflammation to establish allergen-tolerance in the respiratory mucosa (6). Furthermore, manipulation of steroid responsiveness in Tregs could represent a novel strategy to treat steroid refractory asthma, as their responsiveness determines steroid sensitivity during allergic airway inflammation (7).…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Yuan²,

Chen³

et al. 2022

Front. Immunol.

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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.

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Schisandrin B promotes Foxp3+ regulatory T cell expansion by activating heme oxygenase-1 in dendritic cells and exhibits immunomodulatory effects in Th2-mediated allergic asthma

Cited by 11 publications

References 49 publications

Heme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection

Heme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection

Regulatory T-cells in asthma

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

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