Dectin-1 Controls TSLP-Induced Th2 Response by Regulating STAT3, STAT6, and p50-RelB Activities in Dendritic Cells

Gu, Chao; Upchurch, Katherine; Horton, Joshua; Wiest, Mathew; Zurawski, Sandra; Millard, Mark; Kane, Robert R.; Joo, Hye Mee; Miller, Lisa; Oh, Sang Kon

doi:10.3389/fimmu.2021.678036

Cited by 15 publications

(4 citation statements)

References 70 publications

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“…In addition, it has been demonstrated that dectin-1 is downregulated in the epithelium of allergic patients due to the aberrant production of IL-33 [ 33 ]. In line with these results, Gu et al have described that dectin-1 activation suppressed allergic type 2 responses [ 34 ]. Although many research efforts have been made in understanding the role of dectin-1 in the promotion or prevention of type 2 immune responses to allergens, further studies are still needed to fully elucidate its actual role in allergic diseases.…”

Section: The Role Of Clr In the Context Of Allergic Diseasesmentioning

confidence: 54%

C-Type Lectin Receptor Mediated Modulation of T2 Immune Responses to Allergens

Angelina

Martín-Cruz

Rocha-Muñoz

et al. 2023

Curr Allergy Asthma Rep

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Purpose of Review Allergic diseases represent a major health problem of increasing prevalence worldwide. In allergy, dendritic cells (DCs) contribute to both the pathophysiology and the induction of healthy immune responses to the allergens. Different studies have reported that some common allergens contain glycans in their structure. C-type lectin receptors (CLRs) expressed by DCs recognize carbohydrate structures and are crucial in allergen uptake, presentation, and polarization of T cell responses. This review summarizes the recent literature regarding the role of CLRs in the regulation of type 2 immune responses to allergens. Recent Findings In this review, we highlight the capacity of CLRs to recognize carbohydrates in common allergens triggering different signaling pathways involved in the polarization of CD4+ T cells towards specific Th2 responses. Under certain conditions, specific CLRs could also promote tolerogenic responses to allergens, which might well be exploited to develop novel therapeutic approaches of allergen-specific immunotherapy (AIT), the single treatment with potential disease-modifying capacity for allergic disease. At this regard, polymerized allergens conjugated to non-oxidized mannan (allergoid-mannan conjugated) are next-generation vaccines targeting DCs via CLRs that promote regulatory T cells, thus favoring allergen tolerance both in preclinical models and clinical trials. Summary A better understanding of the role of CLRs in the development of allergy and in the induction of allergen tolerance might well pave the way for the design of novel strategies for allergic diseases.

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Section: The Role Of Clr In the Context Of Allergic Diseasesmentioning

confidence: 54%

C-Type Lectin Receptor Mediated Modulation of T2 Immune Responses to Allergens

Angelina

Martín-Cruz

Rocha-Muñoz

et al. 2023

Curr Allergy Asthma Rep

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“…It has been reported that allergenic DC expresses OX40L and IL-6 to communicate with T cells, leading to the expansion of Th2 cells. On the contrary, DC can also produce IL-12 to inhibit allergy, and IL-10 produced by DC or regulatory T cells can downregulate the whole immune responses and thus maintain immune homeostasis ( 24 , 25 ). Consequently, these results demonstrated that OVA triggered the allergenic responses in the spleen cells, especially in the DCs and T cells.…”

Section: Resultsmentioning

confidence: 99%

Establishment of a 3-Dimensional Intestinal Cell Model to Simulate the Intestinal Mucosal Immune System for Food Allergy Investigations

Lin

Wang

et al. 2022

Front. Immunol.

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Food allergy is a worldwide food safety problem with increasing prevalence. Developing novel approaches for food allergy investigations is the basis for controlling food allergies. In this work, a 3-dimensional (3D) intestinal cell model was established to simulate the intestinal mucosal immune system. Gut epithelial cell line CMT93 was cultured in a transwell insert above dendritic cells (DCs) isolated from mouse spleen and stimulated by egg allergen ovalbumin (OVA), then the conditioned media of DCs was transferred to T cells isolated from mouse spleen. The allergy-related indexes of each cell type were determined by qPCR and flow cytometry. Then the TAZ gene was knocked down in the CMT93 cells and the role of the Hippo pathway in OVA-induced food allergy was investigated. The 3D intestinal cell model showed more significant and more specific allergic responses than conventional cell models and is more convenient to be manipulated than the mouse models. This model is an ideal tool for food allergy investigations and would facilitate studies in the field of intestinal mucosal immunity.

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“…The analysis of immune signatures among different CPS groups classified by methodologies A, B, and C revealed several differentially expressed genes that have been linked to various functions in immune regulation. The chemokine XCL1 was shown to predict the response to pembrolizumab in NSCLC ( 31 ), while CCL17 could boost the Th2-type immune response ( 32 ), and both were positively associated with CPS. The genes in the PD-L1-H group that were expressed at lower levels exhibited a negative relation with immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Immunological Characteristics and Genomic Alterations in HPV-Positive Oropharyngeal Squamous Cell Carcinoma Based on PD-L1 Expression

Shi

Xia

et al. 2022

Front. Immunol.

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Programmed death-ligand 1 (PD-L1) expression has been approved as an immune checkpoint inhibitor (ICI) response predictive biomarker; however, the clinicopathological and molecular features of HPV-positive oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] based on PD-L1 expression are not well studied. We aimed to characterize clinicopathological, tumor immune microenvironmental, and molecular features of HPV(+)OPSCC with different PD-L1 expression scored by combined positive score (CPS). A total of 112 cases were collected from 2008-2021 and received PD-L1 and CD8 immunohistochemistry (IHC) staining. 71 samples received DNA sequencing out of which 32 samples received RNA sequencing for immune-related gene alterations or expression analysis. The 32 samples were also subjected to analysis of CD20, CD4, CD8, CD68, Foxp3 and P16 by multiplex immunofluorescence (mIF) staining, and the immune markers were evaluated in the tumor body (TB), tumor margin (TM) and normal stroma (NS) regions separately. Our results showed that of 112 HPV(+)OPSCC tumors, high(CPS≥20), intermediate(1≤CPS<20), and low(CPS<1) PD-L1 expression was seen in 29.5%, 43.8% and 26.8% cases respectively. Non-smoking patients and patients with tumors occurring at the tonsils or having rich lymphocytes infiltration had significantly higher PD-L1 expression. Patients with CPS≥20 had significantly higher tumor mutation burden (TMB, p=0.0058), and PD-L1 expression correlated significantly with CD8+ T cells infiltration, which were ample in tumor regions than in NS in mIF. CD20+, CD4+, CD68+, Foxp3+CD4+ cells were demonstrated to infiltrate higher in TM while CD20+ and CD68+ cells were also enriched in NS and TB regions respectively. However, none of them showed correlations with PD-L1 expression. ARID1A, STK11 alterations were enriched in the low PD-L1 group significantly, while anti-viral immune associated APOBEC mutation signature and immune-related genes expression such as XCL1 and IL11 were positively associated with PD-L1 expression (p<0.05). This is a comprehensive investigation revealing immune and molecular features of HPV(+)OPSCC based on PD-L1 expression. Our study suggested that 73.2% of HPV(+)OPSCC patients may benefit from immunotherapy, and high PD-L1 expression reflects immune-active status of HPV(+)OPSCC accompanied by higher immune effect factors such as TMB, CD8+ cytotoxic T cells and immune-related genomic alterations. Our study offers valuable information for understanding the immune features of HPV(+)OPSCC.

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Dectin-1 Controls TSLP-Induced Th2 Response by Regulating STAT3, STAT6, and p50-RelB Activities in Dendritic Cells

Cited by 15 publications

References 70 publications

C-Type Lectin Receptor Mediated Modulation of T2 Immune Responses to Allergens

C-Type Lectin Receptor Mediated Modulation of T2 Immune Responses to Allergens

Establishment of a 3-Dimensional Intestinal Cell Model to Simulate the Intestinal Mucosal Immune System for Food Allergy Investigations

Analysis of Immunological Characteristics and Genomic Alterations in HPV-Positive Oropharyngeal Squamous Cell Carcinoma Based on PD-L1 Expression

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