Probiotic extracts ameliorate nasal allergy by inducing interleukin‐35‒producing dendritic cells in mice

Xue, Jinmei; Ma, Fei; An, Yun-Fang; Suo, Limin; Geng, Xinyu; Song, Yang; Mo, Li‐Hua; Luo, Xiang‐Qian; Zhang, Xiaowen; liu, Da‐Bo; Zhao, Changqing; Yang, Ping‐Chang

doi:10.1002/alr.22438

Cited by 11 publications

(8 citation statements)

References 30 publications

(33 reference statements)

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“…Secreted by CD4 + FoxP3 + Treg cells, IL-35 plays a central role in AR. IL-35 has a well-defined inhibitory function on AR symptomology [ 46 ], indeed serum IL-35 levels are inversely correlated with the total nasal symptom score (TNSS) in children with AR [ 47 ], and recombinant IL-35 has been used successfully as an exploratory therapeutic in an OVA mouse AR model [ 48 ]. Our results align well with these data in that serum and tissue IL-35 levels are inversely correlated to sneezing, goblet cell infiltration of nasal mucosa, and inflammatory cytokine release resulting from AR.…”

Section: Discussionmentioning

confidence: 99%

Taurine promotes the production of CD4+CD25+FOXP3+ Treg cells through regulating IL-35/STAT1 pathway in a mouse allergic rhinitis model

Zhou

Lü

2021

Allergy Asthma Clin Immunol

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Background Allergic rhinitis (AR) is one of the most widespread immune conditions worldwide. However, common treatments often present with significant side effects or are cost-prohibitive for much of the population. A plethora of treatments have been used for the treatment of AR including antihistamines, steroids, and immune modulators. Among the treatments which have shown potential for efficacy in treating AR with a minimum of side effects but remains understudied is the conditionally essential amino acid taurine. Taurine has been previously shown to reduce AR symptoms. Here, we examine the role of taurine in modulating T regulatory cells, modulating the cytokine response in AR, and restoring healthy nasal mucosa. Methods Blood samples from 20 healthy donors and 20 AR patients were compared for CD4+CD25+FoxP3+ T regulatory (Treg) cell population percentage, cytokine release, and STAT1 signaling with and without taurine treatment or IL-35 neutralization. An OVA-induced AR mouse model was administered vehicle, taurine, or taurine plus an IL-35 neutralizing antibody and assayed for sneezing frequency, inflammatory cytokine response, nasal mucosa goblet cell density, and T regulatory cell percentage. CD4+ cells were further examined for cytokine release, STAT1 phosphorylation, and response to an anti-IL-35 antibody with and without a STAT1 inhibitor. Results Comparison of blood from normal donors and AR patients showed a reduction in CD4+CD25+FoxP3+ Treg cells in AR patients and a strong correlation between Treg percentage and IL-35 release. A similar pattern of Treg suppression was found in untreated AR mice when compared to normal control mice wherein there was a reduction in Treg percentage and a corresponding decrease in IL-35 release. AR mice also demonstrated increased sneezing frequency, an infiltration of goblet cell in nasal mucosa, and a reduction in IL-35 release from CD4+ cells. Conversely, IL-4, IL-5, and IL-13 secretion from CD4+ cells were increased in AR model mice, as was STAT1 phosphorylation. When AR mice were treated with taurine, sneezing frequency and nasal mucosa goblet cell content were reduced while Treg abundance was increased to that of normal mice. Accordingly, IL-35 release was restored, while IL-4, IL-5, and IL-13 secretion from CD4+ cells were suppressed. Likewise, STAT1 phosphorylation was inhibited with taurine treatment. Taurine-treated mice also given an IL-35 neutralizing antibody exhibited AR pathology including frequent sneezing and high nasal goblet cell content while retaining a restoration of Tregs. Furthermore, murine AR model CD4+ cells exposed to recombinant IL-35 responded with a reduction in inflammatory cytokine release and a decrease in STAT1 phosphorylation, mimicking the effect of taurine treatment. Conclusions Taurine induces release of IL-35 in AR; IL-35 promotes the production of CD4+CD25+FoxP3+ Treg cells via a STAT1-dependent pathway. The restoration of Treg populations by taurine normalizes the inflammatory response, reduces AR symptomology, and reduces histopathologic signs of AR.

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Section: Discussionmentioning

confidence: 99%

Taurine promotes the production of CD4+CD25+FOXP3+ Treg cells through regulating IL-35/STAT1 pathway in a mouse allergic rhinitis model

Zhou

Lü

2021

Allergy Asthma Clin Immunol

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“…Secreted by CD4 + FoxP3 + Treg cells, IL-35 plays a central role in AR. IL-35 has a well-de ned inhibitory function on AR symptomology 46 , indeed serum IL-35 levels are inversely correlated with the Total Nasal Symptom Score (TNSS) in children with AR 47 , and recombinant IL-35 has been used successfully as an exploratory therapeutic in an OVA mouse AR model 48 . Our results align well with these data in that serum and tissue IL-35 levels are inversely correlated to sneezing, goblet cell in ltration of nasal mucosa, and in ammatory cytokine release resulting from AR.…”

Section: Discussionmentioning

confidence: 99%

Taurine Promotes the Production of CD4+CD25+FOXP3+ Treg Cells through Regulating IL-35/STAT1 Pathway in a Mouse Allergic Rhinitis Model

Zhou

Lü

et al. 2020

Preprint

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Background: Allergic rhinitis (AR) is one of the most widespread immune conditions worldwide. However, common treatments often present with significant side effects or are cost-prohibitive for much of the population. A plethora of treatments have been used for the treatment of AR including antihistamines, steroids, and immune modulators. Among the treatments which have shown potential for efficacy in treating AR with a minimum of side effects but remains understudied is the conditionally essential amino acid taurine. Taurine has been previously shown to reduce AR symptoms. Here, we examine the role of taurine in modulating T regulatory cells, modulating the cytokine response in AR, and restoring healthy nasal mucosa.Methods: Blood samples from 20 healthy donors and 20 AR patients were compared for CD4+CD25+FoxP3+ T regulatory (Treg) cell population percentage, cytokine release, and STAT1 signaling with and without taurine treatment or IL-35 neutralization. An OVA-induced AR mouse model was administered vehicle, taurine, or taurine plus an IL-35 neutralizing antibody and assayed for sneezing frequency, inflammatory cytokine response, nasal mucosa goblet cell density, and T regulatory cell percentage. CD4+ cells were further examined for cytokine release, STAT1 phosphorylation, and response to an anti-IL-35 antibody with and without a STAT1 inhibitor. Results: Comparison of blood from normal donors and AR patients showed a reduction in CD4+CD25+FoxP3+ Treg cells in AR patients and a strong correlation between Treg percentage and IL-35 release. A similar pattern of Treg suppression was found in untreated AR mice when compared to normal control mice wherein there was a reduction in Treg percentage and a corresponding decrease in IL-35 release. AR mice also demonstrated increased sneezing frequency, an infiltration of goblet cell in nasal mucosa, and a reduction in IL-35 release from CD4+ cells. Conversely, IL-4, IL-5, and IL-13 secretion from CD4+ cells were increased in AR model mice, as was STAT1 phosphorylation. When AR mice were treated with taurine, sneezing frequency and nasal mucosa goblet cell content were reduced while Treg abundance was increased to that of normal mice. Accordingly, IL-35 release was restored, while IL-4, IL-5, and IL-13 secretion from CD4+ cells were suppressed. Likewise, STAT1 phosphorylation was inhibited with taurine treatment. Taurine-treated mice also given an IL-35 neutralizing antibody exhibited AR pathology including frequent sneezing and high nasal goblet cell content while retaining a restoration of Tregs. Furthermore, murine AR model CD4+ cells exposed to recombinant IL-35 responded with a reduction in inflammatory cytokine release and a decrease in STAT1 phosphorylation, mimicking the effect of taurine treatment. Conclusions: Taurine induces release of IL-35 in AR; IL-35 promotes the production of CD4+CD25+FoxP3+ Treg cells via a STAT1-dependent pathway. The restoration of Treg populations by taurine normalizes the inflammatory response, reduces AR symptomology, and reduces histopathologic signs of AR.

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“…This suggests that IL-35 has the potential to induce autologous Breg cells as well as the treatment of autoimmune and inflammatory diseases (18,19). More studies have demonstrated that IL-10-producing dendritic cells induced by IL-35 and phosphorylating STAT3 can induce immunosuppressive property of IL-10-producing B cells (20).…”

Section: Inflammatory Microenvironmentmentioning

confidence: 99%

Regulatory B Cells and Its Role in Central Nervous System Inflammatory Demyelinating Diseases

et al. 2020

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Regulatory B (Breg) cells represent a population of suppressor B cells that participate in immunomodulatory processes and inhibition of excessive inflammation. The regulatory function of Breg cells have been demonstrated in mice and human with inflammatory diseases, cancer, after transplantation, and particularly in autoinflammatory disorders. In order to suppress inflammation, Breg cells produce anti-inflammatory mediators, induce death ligand-mediated apoptosis, and regulate many kinds of immune cells such as suppressing the proliferation and differentiation of effector T cell and increasing the number of regulatory T cells. Central nervous system Inflammatory demyelinating diseases (CNS IDDs) are a heterogeneous group of disorders, which occur against the background of an acute or chronic inflammatory process. With the advent of monoclonal antibodies directed against B cells, breakthroughs have been made in the treatment of CNS IDDs. Therefore, the number and function of B cells in IDDs have attracted attention. Meanwhile, increasing number of studies have confirmed that Breg cells play a role in alleviating autoimmune diseases, and treatment with Breg cells has also been proposed as a new therapeutic direction. In this review, we focus on the understanding of the development and function of Breg cells and on the diversification of Breg cells in CNS IDDs.

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Probiotic extracts ameliorate nasal allergy by inducing interleukin‐35‒producing dendritic cells in mice

Cited by 11 publications

References 30 publications

Taurine promotes the production of CD4+CD25+FOXP3+ Treg cells through regulating IL-35/STAT1 pathway in a mouse allergic rhinitis model

Taurine promotes the production of CD4+CD25+FOXP3+ Treg cells through regulating IL-35/STAT1 pathway in a mouse allergic rhinitis model

Taurine Promotes the Production of CD4+CD25+FOXP3+ Treg Cells through Regulating IL-35/STAT1 Pathway in a Mouse Allergic Rhinitis Model

Regulatory B Cells and Its Role in Central Nervous System Inflammatory Demyelinating Diseases

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