Exposure to Traffic-Related Particulate Matter 2.5 Triggers Th2-Dominant Ocular Immune Response in a Murine Model

Ambient particulate matter (PM), a major component of air pollution, aggravates ocular discomfort and inflammation, similarly to dry eye disease (DED) or allergies. However, the mechanism(s) by which PM induces the ocular inflammatory response is unknown. This study investigated the immunological response of traffic-related fine particulate matter (PM2.5) on the ocular surface in a murine model. C57BL/6 mice were exposed by topical application to PM2.5 or vehicle for 14 days to induce experimental environmental ocular disease. Corneal fluorescein staining and the number of ocular inflammatory cells were assessed in both groups. The expression of IL-1β, IL-6, tumor necrosis factor (TNF)-α, and mucin 5AC (MUC5AC) in the ocular surface were evaluated by real-time PCR. An immunohistochemical assay evaluated apoptosis and goblet cell density. ELISA was used to determine the levels of serum IgE and cytokines of Type 1 helper (Th1) and Type 2 helper (Th2) cells after in vitro stimulation of T cells in the draining lymph nodes (LNs). Exposure to traffic-related PM2.5 significantly increased corneal fluorescein staining and cellular toxicity in the corneal epithelium compared with the vehicle control. A significant increase in the number of CD11b+ cells on the central cornea and mast cells in the conjunctiva was observed in the PM2.5 group. Exposure to PM2.5 was associated with a significant increase in the corneal or conjunctival expression of IL-1β, IL-6, TNF, and MUC5AC compared to the vehicle, and increased maturation of dendric cells (DCs) (MHC-IIhighCD11c+) in draining LNs. In addition, PM2.5 exposure increased the level of serum IgE and Th2 cytokine production in draining LNs on day 14. In conclusion, exposure to traffic-related PM2.5 caused ocular surface damage and inflammation, which induced DC maturation and the Th2-cell-dominant allergic immune response in draining LNs.

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Persimmon-derived tannin ameliorates the pathogenesis of ulcerative colitis in a murine model through inhibition of the inflammatory response and alteration of microbiota

Scientific Reports ◽

10.1038/s41598-021-86608-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Masahiro Kitabatake ◽

Yoko Matsumura ◽

Noriko Ouji-Sageshima ◽

Tatsuki Nishioka ◽

Atsushi Hara ◽

...

Keyword(s):

Ulcerative Colitis ◽

Immune Response ◽

Murine Model ◽

Control Diet ◽

Antimicrobial Activities ◽

Diet Group ◽

Chronic Inflammatory Bowel Disease ◽

Diospyros Kaki ◽

Colon Inflammation

AbstractUlcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) induced by dysregulation of the immune response in the intestinal mucosa. Although the underlying mechanisms of UC development are not fully understood, disruption of gut microbiota, “dysbiosis”, is thought to lead to the development of IBD. Persimmon (Ebenaceae Diospyros kaki Thunb.)-derived tannin, which is a condensed polymeric tannin consisting of catechin groups, has antioxidant, anti-inflammatory, and antimicrobial activities. In this study, we assessed the effect of persimmon-derived tannin on a murine model of UC established by dextran sulfate sodium-induced colitis in female mice. Dietary supplementation of tannin significantly decreased disease activity and colon inflammation. A hydrolysate of tannin directly suppressed expression of inflammatory genes in macrophages in vitro. In faecal microbiota, the relative abundance of Bacteroides was increased significantly by tannin supplementation. Alpha-diversity indices in colitis-induced mice were significantly higher in the tannin diet group compared with the control diet group. Additionally, expansion of Enterobacteriaceae and Enterococcus, which is associated with disease progression of IBD, was remarkably suppressed in the tannin diet group. These results suggest that persimmon-derived tannin ameliorates colon inflammation in UC through alteration of the microbiota composition and immune response, which may be a promising candidate for IBD therapy.

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Effect of overexpression of pparγ on the healing process of corneal alkali burn in mice

AJP Cell Physiology ◽

10.1152/ajpcell.00332.2006 ◽

2007 ◽

Vol 293 (1) ◽

pp. C75-C86 ◽

Cited By ~ 46

Author(s):

Shizuya Saika ◽

Osamu Yamanaka ◽

Yuka Okada ◽

Takeshi Miyamoto ◽

Ai Kitano ◽

...

Keyword(s):

Growth Factors ◽

Ocular Surface ◽

Nuclear Translocation ◽

Healing Process ◽

Inflammatory Cells ◽

Peroxisome Proliferator ◽

Growth Factor Signaling ◽

Alkali Burn

Wound healing involves both local cells and inflammatory cells. Alkali burn of ocular surface tissue is a serious clinical problem often leading to permanent visual impairment resulting from ulceration, scarring and neovascularization during healing. Behaviors of corneal cells and inflammatory cells are orchestrated by growth factor signaling networks that have not been fully uncovered. Here we showed that adenoviral gene introduction of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits activation of ocular fibroblasts and macrophages in vitro and also induced anti-inflammatory and anti-fibrogenic responses in an alkali-burned mouse cornea. PPARγ overexpression suppressed upregulation of inflammation/scarring-related growth factors and matrix metalloproteinases (MMPs) in macrophages. It also suppressed expression of such growth factors and collagen Iα2 and myofibroblast generation upon exposure to TGFβ1. Exogenous PPARγ did not alter phosphorylation of Smad2, but inhibited its nuclear translocation. PPARγ overexpression enhanced proliferation of corneal epithelial cells, but not of fibroblasts in vitro. Epithelial cell expression of MMP-2/-9 and TGFβ1 and its migration were suppressed by PPARγ overexpression. In vivo experiments showed that PPARγ gene introduction suppressed monocytes/macrophages invasion and suppressed the generation of myofibroblasts, as well as upregulation of cytokines/growth factors and MMPs in a healing cornea. In vivo re-epitheliazation with basement membrane reconstruction in the healing, burned, cornea was accelerated by PPARγ-Ad expression, although PPARγ overexpression was considered to be unfavorable for cell migration. Together, these data suggest that overexpression of PPARγ may represent an effective new strategy for treatment of ocular surface burns.

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Reciprocal Protective Immunity againstBordetella pertussis and Bordetella parapertussis in a Murine Model of Respiratory Infection

Infection and Immunity ◽

10.1128/iai.69.11.6981-6986.2001 ◽

2001 ◽

Vol 69 (11) ◽

pp. 6981-6986 ◽

Cited By ~ 25

Author(s):

Mineo Watanabe ◽

Masaaki Nagai

Keyword(s):

Immune Response ◽

Respiratory Infection ◽

Murine Model ◽

Protective Immunity ◽

Interferon Γ ◽

Interleukin 4 ◽

Spleen Cells ◽

Bordetella Parapertussis ◽

Ifn Γ

ABSTRACT The protective immunity induced by infection with Bordetella pertussis and with Bordetella parapertussis was examined in a murine model of respiratory infection. Convalescent mice that had been infected by aerosol with B. pertussis or with B. parapertussis exhibited a protective immune response against B. pertussis and also against B. parapertussis. Anti-filamentous hemagglutinin (anti-FHA) serum immunoglobulin G (IgG) and anti-FHA lung IgA antibodies were detected in both mice infected with B. pertussis and those infected with B. parapertussis. Antibodies against pertussis toxin (anti-PT) and against killed B. pertussis cells were detected in mice infected with B. pertussis. Pertactin-specific antibodies and antibodies against killed B. parapertussis cells were detected in mice infected with B. parapertussis. Spleen cells from mice infected with B. pertussis secreted interferon-γ (IFN-γ) in response to stimulation by FHA or PT. Spleen cells from mice infected with B. parapertussis also secreted IFN-γ in response to FHA. Interleukin-4 was not produced in response to any of the antigens tested. The profiles of cytokine secretion in vitro revealed induction of a Th1-biased immune response during convalescence from infection by B. pertussis and byB. parapertussis. It is possible that Th1 and Th2 responses against FHA might be related to the reciprocal protection achieved in our murine model.

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Preserved T-cell Response in anti-CD20 Treated Multiple Sclerosis Patients Following SARS-CoV-2 Vaccination

10.21203/rs.3.rs-1109886/v1 ◽

2021 ◽

Author(s):

Simon Faissner ◽

Neele Heitmann ◽

Ricarda Rohling ◽

Ulas Ceylan ◽

Marielena Bongert ◽

...

Keyword(s):

Multiple Sclerosis ◽

Immune Response ◽

T Cell ◽

B Cell ◽

T Cell Response ◽

Th2 Cells ◽

Multiple Sclerosis Patients ◽

Cellular Immune ◽

Cell Repopulation

Abstract The SARS-CoV-2 pandemic has tremendous implications for the management of patients with autoimmune conditions such as multiple sclerosis (MS) under immune therapies targeting CD20+ B cells (aCD20). We here investigated humoral and cellular immune responses, including neutralization against SARS-CoV-2 WT and delta variant and T cell responses of aCD20-treated MS patients following SARS-CoV-2 vaccination compared to healthy controls. aCD20-treated MS patients had lower anti-SARS-CoV-2-Spike titers, which correlated with B-cell repopulation. Sera of aCD20 treated patients had reduced capacity to neutralize WT and delta pseudoviruses in vitro. On the contrary, aCD20 treated patients elicited higher frequencies of CD3+ T cells, Th1 cells, Th2 cells, Tc1 cells and CD8+IFN-γ+IL-2+ cells. In summary, aCD20 treated patients have a reduced humoral immune response, depending on B cell repopulation, in accordance with a shift of cellular immune response to a stronger Th1, Th2 and Tc1 phenotype, suggesting strong cellular protection against SARS-CoV-2.

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The Anti-asthmatic Effect of Intratracheally Treated Mesenchymal Stem Cells via Modulation of Lung Macrophage Activation

10.21203/rs.3.rs-91543/v1 ◽

2020 ◽

Author(s):

Hanbit Kang ◽

Yosep Mo ◽

Jaewoo Shin ◽

Hye Young Kim ◽

Sang-Heon Cho ◽

...

Keyword(s):

Stem Cells ◽

Macrophage Activation ◽

Ex Vivo ◽

Macrophage Polarization ◽

Inflammatory Cells ◽

Th2 Cells ◽

Clinical Effects ◽

Asthma Model ◽

Th2 Inflammation

Abstract BackgroundMesenchymal stem cells (MSCs) possess immunomodulatory properties that provide therapeutic potential for the treatment of inflammatory diseases. While the therapeutic and clinical effects of MSCs are partially known, the effects of its administration to the airway in asthma, a chronic airway inflammatory disease, remain unclear.MethodsSix-week-old female BALB/c mice were sensitized and challenged with ovalbumin. The effects of intratracheally administered umbilical cord MSCs were evaluated by measuring airway hyperresponsiveness, airway inflammatory cell analysis, histological analysis, flow cytometry, and quantitative real-time PCR. Furthermore, ex vivo experiments confirmed the effect of MSC treatment on macrophages that originated from bronchoalveolar lavage fluid and were treated with interleukin (IL)-4 to induce M2 activation. Additionally, an in vitro transwell assay confirmed the effect of MSCs on macrophage activation through direct or indirect treatment using the CRL-2019 alveolar macrophage (AM) cell line.ResultsIntratracheal administration of MSCs significantly decreased the elevated levels of inflammatory cells and airway resistance in the murine asthma model. MSC administration also significantly decreased the numbers of Th2 cells, ILC2, and macrophages in the lungs of asthmatic mice. In particular, MHCII and CD86 expression was prominently reduced in dendritic cells and AMs following MSC treatment. Suppressed SiglecF+CD11c+CD11b- resident AMs, presenting strong negative correlation with type II inflammatory cells such as Th2 cells, ILC2, and eosinophils, were restored by intratracheal MSC treatment. Typical macrophage polarization to M2, particularly M2a, was significantly diminished. Expression levels of markers presenting M2 polarization and Th2 inflammation were decreased in the asthma model upon MSC administration. Ex vivo experiments of IL-4 treated AMs confirmed that MSC treatment reduced Il-12 and Tnfa expression as well as that of M2 markers such as Cd206 and Retnla. In vitro experiments of IL-4 treated AMs confirmed that both direct and indirect MSC treatments through transwells significantly reduced Il-5 and Il-13 expression. No difference between the two treatment methods was found.ConclusionsUmbilical cord MSCs appear to regulate pulmonary macrophages, suppress Th2 inflammation, and mediate anti-asthmatic effects via soluble mediators.

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Traffic Derived Particulate Matter Triggers Ocular Surface Inflammation in Murine Model

Proceedings of the 4th World Congress on New Technologies ◽

10.11159/icepr18.185 ◽

2018 ◽

Author(s):

Hyun Soo Lee ◽

Ji Young Kwon ◽

Sehyun Han ◽

Ki-Jun Jeon

Keyword(s):

Particulate Matter ◽

Murine Model ◽

Ocular Surface ◽

Surface Inflammation ◽

Ocular Surface Inflammation

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PM2.5 Mediated Alterations In The In Vitro Human Granuloma Resulting In Reactivation Of Mycobacteria

10.21203/rs.3.rs-568825/v1 ◽

2021 ◽

Author(s):

Athisankaran Punniyamurthy ◽

Sumedha Sharma ◽

Khushpreet Kaur ◽

Uma Nahar Saikia ◽

Ravindra Khaiwal ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Particulate Matter ◽

Mycobacterium Bovis ◽

Bacterial Load ◽

Granuloma Formation ◽

Human Pbmcs ◽

Cytokine Levels ◽

Mycobacterial Antigens

Abstract Exposure to pollutants diminishes the immune response to mycobacterial antigens relevant to contain the infection in the granuloma, thus leading to reactivation of latent bacilli. Present study was therefore designed based on the hypothesis that exposure to particulate matter pollutant PM2.5 affects the granuloma formation and reactivation of latent mycobacterial bacilli contained in the granuloma. For the extraction of PM2.5, based on initial standardizations, teflon filter was selected over the quartz filter. Two different approaches were used to study the effect of PM2.5 on the human PBMCs granuloma formed by Mycobacterium bovis BCG at MOI 0.1. In the first approach, granuloma formed in the presence of PM2.5 was loosely packed and ill-defined with significant downregulation of dormancy associated mycobacterial genes, upregulation of reactivation associated rpfB gene along with a significant increase in TNFα level without any change in the bacterial load in terms of CFUs. In the second approach, PM2.5 treatment of already established human PBMCs granuloma formed with M. bovis BCG also led to its disruption. Although, in these conditions, downregulation of dormancy associated genes was observed but there was also a decrease in the expression of reactivation associated rpfB gene without any change in the cytokine levels. Therefore, it can be inferred that in the presence of PM2.5, there is poor granuloma formation along with a change in mycobacterial gene expression characteristics of active bacilli and alteration in host immune response without any significant changes following treatment of already established granuloma with the pollutant.

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Comparative Immune Response to PE and PE_PGRS Antigens of Mycobacterium tuberculosis

Infection and Immunity ◽

10.1128/iai.69.9.5606-5611.2001 ◽

2001 ◽

Vol 69 (9) ◽

pp. 5606-5611 ◽

Cited By ~ 140

Author(s):

Giovanni Delogu ◽

Michael J. Brennan

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Immunological Response ◽

Humoral Response ◽

Immune Recognition ◽

Entire Genome ◽

Humoral Immune ◽

Amino Terminal ◽

C Terminus

ABSTRACT Sequencing of the entire genome of Mycobacterium tuberculosis identified a novel multigene family composed of two closely related subfamilies designated PE and PE_PGRS. The major difference between these two families is the presence of a domain containing numerous Gly-Ala repeats extending to the C terminus of the PE_PGRS genes. We have used a representative PE_PGRS gene fromM. tuberculosis, Rv1818c(1818PE_PGRS), and its amino-terminal PE region (1818PE), to investigate the immunological response to these proteins during experimental tuberculosis and following immunization with DNA constructs. During infection of mice with M. tuberculosis, a significant humoral immune response was observed against recombinant 1818PE_PGRS but not toward the 1818PE protein. Similarly, immunization with a 1818PE_PGRS DNA construct induced antibodies directed against 1818PE_PGRS but not against 1818PE proteins, and no humoral response was induced by 1818PE DNA. These results suggest that certain PE_PGRS genes are expressed during infection of the host with M. tuberculosis and that an antibody response is directed solely against the Gly-Ala-rich PGRS domain. Conversely, splenocytes from 1818PE-vaccinated mice but not mice immunized with 1818PE_PGRS secreted gamma interferon following in vitro restimulation and demonstrated protection in the mouse tuberculosis challenge model. These results suggest that the PE vaccine can elicit an effective cellular immune response and that immune recognition of the PE antigen is influenced by the Gly-Ala-rich PGRS domain.

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Lack of WDFY4 Aggravates Ovalbumin-Induced Asthma via Enhanced Th2 Cell Differentiation

International Archives of Allergy and Immunology ◽

10.1159/000516970 ◽

2021 ◽

pp. 1-8

Author(s):

Yan Li ◽

Anran Wang ◽

Feng Long ◽

Fei Gao ◽

Shang Gao ◽

...

Keyword(s):

Cell Differentiation ◽

Susceptibility Gene ◽

Inflammatory Cells ◽

Lavage Fluid ◽

Th2 Cells ◽

Th2 Cytokines ◽

Wild Type ◽

Th2 Cell ◽

Study Results

Background: Asthma is a chronic inflammatory airway disease, and Th2 cells play an important role in asthma. WDFY4 (WDFY family member 4) is a susceptibility gene in several autoimmune diseases. Objective: In this study, the roles of WDFY4 in Th2 cell differentiation and Th2-dependent asthma were investigated. Methods: Naïve CD4+ T cells were isolated from wild-type and WDFY4-deficient mice and induced to differentiate in vitro. Subsequently, a mouse model of asthma was established by sensitization with ovalbumin. Results: Study results showed that WDFY4 deficiency could promote the differentiation of Th2 cells and the production of Th2 cytokines. WDFY4-deficient asthmatic mice showed higher levels of Th2 cytokines in the lungs and bronchoalveolar lavage fluid than wild-type mice. Moreover, infiltration of inflammatory cells, hyperplasia of goblet cells, production of mucus, and deposition of collagen were enhanced in WDFY4-deficient asthmatic mice. Conclusions: Our study demonstrates the pivotal role of WDFY4 in the pathogenesis of asthma and in Th2 cell differentiation.

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