Possible Involvement of Type 2 Cytokines in Alloknesis in Mouse Models of Menopause and Dry Skin

2021 ◽  
Author(s):  
Nao Ichimasu ◽  
Yue Chen ◽  
Keisuke Kobayashi ◽  
So Suzuki ◽  
Sakiko Chikazawa ◽  
...  
Keyword(s):  
Mouse Models ◽  
Dry Skin ◽  
Type 2 Cytokines

scholarly journals Comparative Transcriptomics of IBD Patients Indicates Induction of Type 2 Immunity Irrespective of the Disease Ideotype

2021 ◽  
Vol 8 ◽  
Author(s):  
Miguel Gonzalez Acera ◽  
Jay V. Patankar ◽  
Leonard Diemand ◽  
Britta Siegmund ◽  
Markus F. Neurath ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mouse Models ◽  
Intestinal Inflammation ◽  
Mucosal Healing ◽  
Th2 Cells ◽  
Parasitic Infections ◽  
Inflammatory Conditions ◽  
Elevated Type ◽  
Type 2 Cytokines

Inflammatory cytokines initiate and sustain the perpetuation of processes leading to chronic inflammatory conditions such as inflammatory bowel diseases (IBD). The nature of the trigger causing an inflammatory reaction decides whether type 1, type 17, or type 2 immune responses, typically characterized by the respective T- helper cell subsets, come into effect. In the intestine, Type 2 responses have been linked with mucosal healing and resolution upon an immune challenge involving parasitic infections. However, type 2 cytokines are frequently elevated in certain types of IBD in particular ulcerative colitis (UC) leading to the assumption that Th2 cells might critically support the pathogenesis of UC raising the question of whether such elevated type 2 responses in IBD are beneficial or detrimental. In line with this, previous studies showed that suppression of IL-13 and other type 2 related molecules in murine models could improve the outcomes of intestinal inflammation. However, therapeutic attempts of neutralizing IL-13 in ulcerative colitis patients have yielded no benefits. Thus, a better understanding of the role of type 2 cytokines in regulating intestinal inflammation is required. Here, we took a comparative transcriptomic approach to address how Th2 responses evolve in different mouse models of colitis and human IBD datasets. Our data show that type 2 immune-related transcripts are induced in the inflamed gut of IBD patients in both Crohn's disease and UC and across widely used mouse models of IBD. Collectively our data implicate that the presence of a type 2 signature rather defines a distinct state of intestinal inflammation than a disease-specific pathomechanism.

scholarly journals Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eva Conde ◽  
Romain Bertrand ◽  
Bianca Balbino ◽  
Jonathan Bonnefoy ◽  
Julien Stackowicz ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Mouse Models ◽  
Cost Effective ◽  
Interleukin 4 ◽  
Mucus Production ◽  
Post Vaccination ◽  
Type 2 Cytokines ◽  
Therapeutic Monoclonal Antibodies

AbstractAllergic asthma is characterized by elevated levels of IgE antibodies, type 2 cytokines such as interleukin-4 (IL-4) and IL-13, airway hyperresponsiveness (AHR), mucus hypersecretion and eosinophilia. Approved therapeutic monoclonal antibodies targeting IgE or IL-4/IL-13 reduce asthma symptoms but require costly lifelong administrations. Here, we develop conjugate vaccines against mouse IL-4 and IL-13, and demonstrate their prophylactic and therapeutic efficacy in reducing IgE levels, AHR, eosinophilia and mucus production in mouse models of asthma analyzed up to 15 weeks after initial vaccination. More importantly, we also test similar vaccines specific for human IL-4/IL-13 in mice expressing human IL-4/IL-13 and the related receptor, IL-4Rα, to find efficient neutralization of both cytokines and reduced IgE levels for at least 11 weeks post-vaccination. Our results imply that dual IL-4/IL-13 vaccination may represent a cost-effective, long-term therapeutic strategy for the treatment of allergic asthma as demonstrated in mouse models, although additional studies are warranted to assess its safety and feasibility.

scholarly journals Maintenance of Type 2 Response by CXCR6-Deficient ILC2 in Papain-Induced Lung Inflammation

2019 ◽  
Vol 20 (21) ◽  
pp. 5493 ◽  
Author(s):  
Meunier ◽  
Chea ◽  
Garrido ◽  
Perchet ◽  
Petit ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Nk Cell ◽  
Lymphoid Cells ◽  
Inflammatory Conditions ◽  
Airway Diseases ◽  
Type 2 Cytokines ◽  
Lymphoid Organogenesis ◽  
Deficient Mice

Innate lymphoid cells (ILC) are important players of early immune defenses in situations like lymphoid organogenesis or in case of immune response to inflammation, infection and cancer. Th1 and Th2 antagonism is crucial for the regulation of immune responses, however mechanisms are still unclear for ILC functions. ILC2 and NK cells were reported to be both involved in allergic airway diseases and were shown to be able to interplay in the regulation of the immune response. CXCR6 is a common chemokine receptor expressed by all ILC, and its deficiency affects ILC2 and ILC1/NK cell numbers and functions in lungs in both steady-state and inflammatory conditions. We determined that the absence of a specific ILC2 KLRG1+ST2– subset in CXCR6-deficient mice is probably dependent on CXCR6 for its recruitment to the lung under inflammation. We show that despite their decreased numbers, lung CXCR6-deficient ILC2 are even more activated cells producing large amount of type 2 cytokines that could drive eosinophilia. This is strongly associated to the decrease of the lung Th1 response in CXCR6-deficient mice.

scholarly journals Regulation of bronchial epithelial barrier integrity by type 2 cytokines and histone deacetylases in asthmatic patients

2017 ◽  
Vol 139 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Paulina Wawrzyniak ◽  
Marcin Wawrzyniak ◽  
Kerstin Wanke ◽  
Milena Sokolowska ◽  
Kreso Bendelja ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Epithelial Barrier ◽  
Bronchial Epithelial ◽  
Barrier Integrity ◽  
Asthmatic Patients ◽  
Type 2 Cytokines

scholarly journals A type 2 cytokine axis for thymus emigration

2017 ◽  
Vol 214 (8) ◽  
pp. 2205-2216 ◽  
Author(s):  
Andrea J. White ◽  
Song Baik ◽  
Sonia M. Parnell ◽  
Amanda M. Holland ◽  
Frank Brombacher ◽  
...  
Keyword(s):  
T Cells ◽  
Stromal Cells ◽  
Perivascular Spaces ◽  
Thymocyte Development ◽  
Invariant Nkt Cells ◽  
Developmental Program ◽  
Innate T Cells ◽  
Type 2 Cytokines ◽  
Thymic Stromal Cells

In the thymus, stromal microenvironments support a developmental program that generates mature T cells ready for thymic exit. The cellular and molecular specialization within thymic stromal cells that enables their regulation of specific stages of thymocyte development is poorly understood. Here, we show the thymic microenvironment expresses the type 2 IL-4R complex and is functionally responsive to its known ligands, IL-4 and IL-13. Absence of IL-4Rα limits thymocyte emigration, leading to an intrathymic accumulation of mature thymocytes within medullary perivascular spaces and reduced numbers of recent thymic emigrants. Thymus transplantation shows this requirement maps to IL-4Rα expression by stromal cells, and we provide evidence that it regulates thymic exit via a process distinct from S1P-mediated migration. Finally, we reveal a cellular mechanism by which IL-4+IL-13+ invariant NKT cells are necessary for IL-4Rα signaling that regulates thymic exit. Collectively, we define a new axis for thymic emigration involving stimulation of the thymic microenvironment via type 2 cytokines from innate T cells.

Mouse Models of Type 2 Diabetes

2001 ◽  
pp. 191-205
Author(s):  
Domenico Accili ◽  
Byung-Chul Park
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Models

scholarly journals Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

2020 ◽  
Author(s):  
Ming Wang ◽  
Xiangting Bu ◽  
Ge Luan ◽  
Liqing Lin ◽  
Yang Wang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Nasal Polyps ◽  
Acid Metabolism ◽  
Distinct Type ◽  
Arachidonic Acid Metabolism ◽  
Eosinophil Infiltration ◽  
Phenotypic Traits ◽  
Molecular Signatures ◽  
Type 2 Cytokines

Abstract Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid asthma have more severe disease and are difficult to treat. However, the molecular endotypes associated with CRSwNP with comorbid asthma (CRSwNP+AS) are not clear. This study aimed to investigate the characteristics of type 2 inflammation and the molecular signatures associated with CRSwNP+AS. Methods: A total of 195 subjects; including 65 CRSwNP+AS patients, 99 patients with CRSwNP-alone, and 31 healthy control subjects; were enrolled in the study. Nasal tissues from patients with CRSwNP+AS, CRSwNP-alone and control subjects were assessed for infiltration of inflammatory cells and concentrations of total IgE. Whole-transcriptome sequencing was performed and differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) and their associated pathways were analyzed. The correlations between type 2 cytokines and local eosinophils, tissue IgE, and transcriptome signatures were evaluated. Results: Significantly higher local eosinophil infiltration and higher levels of total IgE were found in nasal tissues from CRSwNP+AS patients than in nasal tissues from CRSwNP-alone patients. Furthermore, atopy and recurrence were significantly more frequent in patients with CRSwNP+AS than in patients with CRSwNP-alone (62.5% vs 28.6% and 66.7% vs 26.9%, respectively). RNA sequencing analysis identified 1988 common DE-mRNAs, and 176 common DE-lncRNAs shared by CRSwNP+AS versus control and CRSwNP-alone versus control. Weighted gene coexpression network analysis (WGCNA) identified LINC01146 as hub lncRNA dysregulated in both subtypes of CRSwNP. Overall, 968 DE-mRNAs and 312 DE-lncRNAs were identified between CRSwNP+AS and CRSwNP-alone. Both pathway enrichment analysis and WGCNA indicated that the phenotypic traits of CRSwNP+AS were mainly associated with higher activities of arachidonic acid metabolism, type 2 cytokines related pathway and fibrinolysis pathway, and lower activity of IL-17 signalling pathway. Furthermore, the expression of type 2 cytokines; IL5 and IL13, was positively correlated with local eosinophil infiltration, tissue IgE level, and the expression of DE-mRNAs that related to arachidonic acid metabolism. Moreover, WGCNA identified HK3-006 as hub lncRNA in yellow module that most positively correlated with phenotypic traits of CRSwNP+AS. Conclusions: Patients with CRSwNP+AS have distinct type 2-high inflammation-associated molecular signatures in nasal tissues compared to patients with CRSwNP-alone.

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