scholarly journals Treatment with an Anti-CX3CL1 Antibody Suppresses M1 Macrophage Infiltration in Interstitial Lung Disease in SKG Mice

2021 ◽  
Vol 14 (5) ◽  
pp. 474
Author(s):  
Satoshi Mizutani ◽  
Junko Nishio ◽  
Kanoh Kondo ◽  
Kaori Motomura ◽  
Zento Yamada ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
M2 Macrophages ◽  
Inhibitory Effects ◽  
M1 Macrophages ◽  
Immune Mediated ◽  
M1 Macrophage ◽  
Bronchoalveolar Fluid ◽  
Chemokine Ligand ◽  
Cx3cr1 Expression

CX3C Motif Chemokine Ligand 1 (CX3CL1; fractalkine) has been implicated in the pathogenesis of rheumatoid arthritis (RA) and its inhibition was found to attenuate arthritis in mice as well as in a clinical trial. Therefore, we investigated the effects of an anti-CX3CL1 monoclonal antibody (mAb) on immune-mediated interstitial lung disease (ILD) in SKG mice, which exhibit similar pathological and clinical features to human RA-ILD. CX3CL1 and CX3C chemokine receptor 1 (CX3CR1), the receptor for CX3CL1, were both expressed in the fibroblastic foci of lung tissue and the number of bronchoalveolar fluid (BALF) cells was elevated in ILD in SKG mice. No significant changes were observed in lung fibrosis or the number of BALF cells by the treatment with anti-CX3CL1 mAb. However, significantly greater reductions were observed in the number of M1 macrophages than in M2 macrophages in the BALF of treated mice. Furthermore, CX3CR1 expression levels were significantly higher in M1 macrophages than in M2 macrophages. These results suggest the stronger inhibitory effects of the anti-CX3CL1 mAb treatment against the alveolar infiltration of M1 macrophages than M2 macrophages in ILD in SKG mice. Thus, the CX3CL1-CX3CR1 axis may be involved in the infiltration of inflammatory M1 macrophages in RA-ILD.

scholarly journals Hydrogen Promotes the M1 Macrophage Conversion During the Polarization of Macrophages in Necrotizing Enterocolitis

2021 ◽  
Vol 9 ◽  
Author(s):  
Shenghua Yu ◽  
ZhiBao Lv ◽  
Zhimei Gao ◽  
Jingyi Shi ◽  
Qingfeng Sheng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lamina Propria ◽  
Necrotizing Enterocolitis ◽  
Nuclear Factor Κb ◽  
Inflammatory Factors ◽  
Nuclear Factor ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
M1 And M2 Macrophages

Background: Hydrogen is protective against intestinal injury in necrotizing enterocolitis (NEC), mainly through to alleviate inflammation response. The M1 macrophages can promote inflammation. We hypothesized that hydrogen would promote the M1 macrophages conversion during the polarization and reduce the inflammatory factors in NEC.Methods: We used M1 and M2 macrophages induced from RAW264.7 cells and bone marrow-derived macrophages, models of NEC and macrophages derived from spleens, abdominal lymph nodes and lamina propria in model mice. Cytokines, CD16/32 and CD206 were measured by quantitative PCR, flow cytometry. Nuclear factor-κB (NF-κB) p65 were determined by western blot. Histology staining were used to assess the severity of NEC.Results: Macrophages were successfully polarized to M1 or M2 by assessing the expression of inflammatory factors. Pro-inflammatory factors and CD16/32 in M1 macrophages were decreased, and the expression of CD16/32 in lamina propria were inhibited after treatment with hydrogen, but the changes has no effects in other tissues. Hydrogen inhibited the NF-κB p65 in M1 macrophages nucleus and distal ileum of NEC. HE staining showed hydrogen could attenuate the severity of NEC.Conclusion: Hydrogen could attenuate the severity of NEC through promoting M1 macrophages conversion by inhibited the expression of NF-κB p65 in the nucleus.

scholarly journals Aberrantly Expressed Galectin-9 Is Involved in the Immunopathogenesis of Anti-MDA5-Positive Dermatomyositis-Associated Interstitial Lung Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Lin Liang ◽  
Ya-Mei Zhang ◽  
Ya-Wen Shen ◽  
Ai-Ping Song ◽  
Wen-Li Li ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Disease Activity ◽  
Lung Disease ◽  
Longitudinal Studies ◽  
Type I ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Necrotizing Myopathy ◽  
Immune Mediated

BackgroundDermatomyositis (DM) associated rapidly progressive interstitial lung disease (RP-ILD) has high mortality rate and poor prognosis. Galectin-9 (Gal-9) plays multiple functions in immune regulation. We investigated Gal-9 expression in DM patients and its association with DM-ILD.MethodsA total of 154 idiopathic inflammatory myopathy patients and 30 healthy controls were enrolled in the study. Cross-sectional and longitudinal studies were used to analyze the association between serum Gal-9 levels and clinical features. Enzyme-linked immunosorbent assay and qRT-PCR were used to examine Gal-9 expression in the sera and isolated peripheral blood mononuclear cells (PBMCs) from DM patients. Immunohistochemistry was performed to analyze the expression of Gal-9 and its ligand (T-cell immunoglobulin mucin (Tim)-3 and CD44) in lung tissues from anti-melanoma differentiation-associated gene 5 (MDA5)-positive patients. The effect of Gal-9 on human lung fibroblasts (MRC-5) was investigated in vitro.ResultsSerum Gal-9 levels were significantly higher in DM patients than in immune-mediated necrotizing myopathy patients and healthy controls (all p < 0.001). Higher serum Gal-9 levels were observed in anti-MDA5-positive DM patients than in anti-MDA5-negative DM patients [33.8 (21.9–44.7) vs. 16.2 (10.0–26.9) ng/mL, p < 0.001]. Among the anti-MDA5-positive DM patients, serum Gal-9 levels were associated with RP-ILD severity. Serum Gal-9 levels were significantly correlated with disease activity in anti-MDA5-positive DM patients in both cross-sectional and longitudinal studies. PBMCs isolated from anti-MDA5-positive DM patients (3.7 ± 2.3 ng/mL) produced higher levels of Gal-9 than those from immune-mediated necrotizing myopathy patients (1.1 ± 0.3 ng/mL, p = 0.022) and healthy controls (1.4 ± 1.2 ng/mL, p = 0.045). The mRNA levels of Gal-9 were positively correlated with the levels of type-I interferon-inducible genes MX1 (r = 0.659, p = 0.020) and IFIH1 (r = 0.787, p = 0.002) in PBMCs from anti-MDA5-positive DM patients. Immunohistochemistry revealed increased Gal-9 and Tim-3 expression in the lung tissues of patients with DM and RP-ILD. In vitro stimulation with Gal-9 protein increased CCL2 mRNA expression in MRC-5 fibroblasts.ConclusionsAmong anti-MDA5-positive DM patients, Gal-9 could be a promising biomarker for monitoring disease activity, particularly for RP-ILD severity. Aberrant expression of the Gal-9/Tim-3 axis may be involved in the immunopathogenesis of DM-ILD.

scholarly journals Interstitial lung disease is not rare in immune-mediated necrotizing myopathy with anti-signal recognition particle antibodies

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yongpeng Ge ◽  
Hanbo Yang ◽  
Xinyue Xiao ◽  
Lin Liang ◽  
Xin Lu ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
Signal Recognition Particle ◽  
Ground Glass Opacity ◽  
Signal Recognition ◽  
High Resolution Computed Tomography ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Long Term Follow Up

Abstract Objectives The purpose was to clarify the characteristics of interstitial lung disease (ILD) in immune-mediated necrotizing myopathy (IMNM) patients with anti-signal recognition particle (SRP) antibodies. Methods Medical records of IMNM patients with anti-SRP antibodies were reviewed retrospectively. Results A total of 60 patients were identified. Twenty-seven (45.0%) patients were diagnosed with ILD based on lung imaging: nonspecific interstitial pneumonia (NSIP) in 17 patients (63.0%) and organizing pneumonia in 9 patients (33.3%). Reticulation pattern was identified in 17 patients (63.0%) whereas 10 cases (37.0%) showed ground glass opacity and patchy shadows by high-resolution computed tomography (HRCT). Pulmonary function tests (PFTs) were available in 18 patients, 6 (33.3%) and 10 (55.6%) patients were included in the mild and moderate group, respectively. The average age at the time of ILD onset was significantly older than those without ILD (48.6 ± 14.4 years vs. 41.2 ± 15.4 years, p < 0.05), and the frequency of dysphagia in the ILD group was higher than the group without ILD (p < 0.05). Long-term follow-up was available on 9 patients. PFTs were stable in 8 (88.9%), and the HRCT remained stable in 6 (66.7%) patients. Conclusions ILD is not rare in IMNM patients with anti-SRP antibodies, most being characterized as mild to moderate in severity. NSIP is the principal radiologic pattern, and ILD typically remains stable following treatment.

scholarly journals Aberrantly Expressed Galectin-9 is Involved in the Immunopathogenesis of anti-MDA5-Positive Dermatomyositis-Associated Interstitial Lung Disease

2020 ◽  
Author(s):  
Lin Liang ◽  
Ya-Mei Zhang ◽  
Ya-Wen Shen ◽  
Ai-Ping Song ◽  
Wen-Li Li ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Disease Activity ◽  
Lung Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Necrotizing Myopathy ◽  
Immune Mediated

Abstract Background: Rapidly progressive interstitial lung disease (RP-ILD) has high mortality rate and poor prognosis. Galectin-9 (Gal-9) plays multiple functions in immune regulation. We investigated Gal-9 expression in patients with dermatomyositis (DM) and the impact of Gal-9 on the development of DM-ILD. Methods: Enzyme-linked immunosorbent assay and qRT-PCR were used to examine Gal-9 expression in the sera and isolated peripheral blood mononuclear cells (PBMCs) from patients with DM. Immunohistochemistry was performed to analyze the expression of Gal-9 and its ligand (T-cell immunoglobulin mucin (Tim)-3 and CD44) in lung tissues from patients who were positive for anti-melanoma differentiation-associated gene 5 (MDA5). The effect of Gal-9 on human lung fibroblasts (MRC-5) was also investigated in vitro. Results: Serum Gal-9 levels were significantly higher in patients with DM than in those with immune-mediated necrotizing myopathy and healthy controls (p < 0.001). Higher levels of serum Gal-9 were observed in anti-MDA5-positive patients with DM than in anti-MDA5-negative patients with DM (33.8 (21.9–44.7) vs 16.2 (10.0–26.9) ng/mL, p < 0.001). Among the anti-MDA5-positive patients with DM, serum Gal-9 levels were associated with ILD severity. Serum Gal-9 levels were significantly correlated with disease activity in anti-MDA5-positive patients with DM in both cross-sectional and longitudinal studies. PBMCs isolated from anti-MDA5-positive patients with DM (3.7 ± 2.3 ng/mL) produced higher levels of Gal-9 than those from patients with immune-mediated necrotizing myopathy (1.1 ± 0.3 ng/mL, p = 0.022) and healthy controls (1.4 ± 1.2 ng/mL, p = 0.045). The mRNA levels of Gal-9 were positively correlated with levels of type-I interferon-inducible genes MX1 (r = 0.659, p = 0.020) and IFIH1 (r = 0.787, p = 0.002) in PBMCs from anti-MDA5-positive patients with DM. Immunohistochemistry revealed increased Gal-9 and Tim-3 expression in the lung tissues of patients with DM and RP-ILD. In vitro stimulation with Gal-9 protein increased CCL2 mRNA expression in MRC-5 fibroblasts.Conclusions: Among anti-MDA5-positive patients with DM, Gal-9 could be a promising biomarker for monitoring disease activity, particularly for RP-ILD severity. Aberrant expression of the Gal-9/Tim-3 axis may be involved in the immunopathogenesis of DM-ILD.

scholarly journals Macrophage Innate Training Induced by IL-4 Activation Enhances OXPHOS Driven Anti-Mycobacterial Responses

2021 ◽  
Author(s):  
Mimmi L. E. Lundahl ◽  
Morgane Mitermite ◽  
Dylan G. Ryan ◽  
Niamh C. Williams ◽  
Ming Yang ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Mycobacterial Infection ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Cytokine Responses ◽  
M1 Macrophage ◽  
Mycobacterial Growth ◽  
Insight Into ◽  
Alternatively Activated ◽  
Classically Activated

AbstractMacrophages are key innate immune cells for determining the outcome of Mycobacterium tuberculosis infection. Polarization with IFNγ and LPS into the “classically activated” M1 macrophage enhances pro-inflammatory and microbicidal responses, important for eradicating the bacterium. By contrast, “alternatively activated” M2 macrophages, polarized with IL-4, oppose bactericidal mechanisms and allow mycobacterial growth. These activation states are accompanied by distinct metabolic profiles, where M1 macrophages favor near exclusive use of glycolysis, whereas M2 macrophages up-regulate oxidative phosphorylation (OXPHOS). Here we demonstrate that activation with IL-4 counterintuitively induces protective innate memory against mycobacterial challenge. This was associated with enhanced pro-inflammatory cytokine responses and killing capacity. Moreover, despite this switch towards a phenotype that is more akin to classical activation, IL-4 trained macrophages do not demonstrate M1-typical metabolism, instead retaining heightened use of OXPHOS. Moreover, inhibition of OXPHOS with oligomycin, 2-deoxy glucose or BPTES all impeded heightened pro-inflammatory cytokine responses from IL-4 trained macrophages. Lastly, this work identifies that IL-10 negatively regulates protective IL-4 training, impeding pro-inflammatory and bactericidal mechanisms. In summary, this work provides new and unexpected insight into alternative macrophage activation states in the context of mycobacterial infection.

scholarly journals Muscular and extramuscular clinical features of patients with anti-PM/Scl autoantibodies

Neurology ◽  
2018 ◽  
Vol 90 (23) ◽  
pp. e2068-e2076 ◽  
Author(s):  
Rebecca De Lorenzo ◽  
Iago Pinal-Fernandez ◽  
Wilson Huang ◽  
Jemima Albayda ◽  
Eleni Tiniakou ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Clinical Features ◽  
Disease Onset ◽  
The Other ◽  
Course Of Disease ◽  
Immune Mediated ◽  
Subcutaneous Edema ◽  
Severe Weakness

ObjectiveTo define the clinical features of myositis patients with anti-PM/Scl-75 and/or anti-PM/Scl-100 autoantibodies at disease onset and during the course of disease and compare them to patients with other forms of myositis.MethodsIn this longitudinal cohort study, the prevalence and severity of clinical features at disease onset and during follow-up were compared between anti-PM/Scl-positive patients and those with the antisynthetase syndrome (AS), dermatomyositis (DM), and immune-mediated necrotizing myopathy (IMNM).ResultsForty-one anti-PM/Scl-positive, 132 AS, 178 DM, and 135 IMNM patients were included. Although muscle weakness was a presenting feature in just 37% of anti-PM/Scl-positive patients, 93% eventually developed weakness. Unlike the other groups, anti-PM-Scl-positive patients had more severe weakness in arm abductors than hip flexors. Interstitial lung disease was a presenting feature in just 10% of anti-PM/Scl-positive patients, but occurred in 61% during follow-up; fewer patients with DM (13%, p < 0.001) and IMNM (6%, p < 0.001) and more patients with AS (80%, p < 0.05) developed interstitial lung disease during the course of disease. Mechanic's hands (80%), Raynaud syndrome (78%), sclerodactyly (66%), telangiectasias (66%), esophageal reflux disease (61%), subcutaneous edema (46%), puffy hands (39%), and calcinosis (39%) occurred more frequently in anti-PM/Scl-positive patients than in the other groups. Although 30% of anti-PM/Scl-positive patients met criteria for systemic sclerosis, less than 5% had renal crisis or finger ulcerations. No differences were found between patients with only anti-PM/Scl-100 or only anti-PM/Scl-75 autoantibodies.ConclusionsUnlike patients with DM, AS, or IMNM, anti-PM/Scl-positive patients have weaker arm abductors than hip flexors. Anti-PM/Scl-positive patients also have the most extensive extramuscular features.

scholarly journals Clinical types of lung disease in polymyositis and dermatomyositis

2021 ◽  
Vol 2 (4) ◽  
pp. 34-39
Author(s):  
Inna B. Bondarenko ◽  
◽  
Liubov A. Ponomareva ◽  
Elena N. Popova ◽  
◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inclusion Body ◽  
Lung Tissue ◽  
Inclusion Body Myositis ◽  
Rapid Development ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Immune Mediated ◽  
Observed Damage

The idiopathic inflammatory myopathies are a group of rare, heterogeneous connective tissue disorders characterized by skeletal muscle inflammation. The four main forms of idiopathic inflammatory myopathies are dermatomyositis, polymyositis, inclusion body myositis, and necrotizing immune-mediated myopathy. Each form of myositis, other than inclusion body myositis, can be associated with damage to many organs, including the lungs, heart, joints, and skin. The most often observed damage to the lung tissue with the development of interstitial lung disease, which occurs with or without myositis. The severity of the course varies from mild to severe, with rapid development of respiratory failure. Interstitial lung disease can be fatal in patients with myositis, therefore, it is necessary to assess the damage to the lung tissue in the early stages of the disease.

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