Expression Of CC Chemokine Ligand 18 Research Articles

Genetic Variation in CCL18 Gene Influences CCL18 Expression and Correlates with Survival in Idiopathic Pulmonary Fibrosis: Part A.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease, characterized by fibroblast proliferation and extracellular matrix deposition. CC-chemokine ligand 18 (CCL18) upregulates the production of collagen by lung fibroblasts and is associated with mortality. This study was designed to evaluate the influence of single nucleotide polymorphisms (SNPs) in the CCL18 gene on CCL18 expression and survival in IPF. Serum CCL18 levels and four SNPs in the CCL18 gene were analyzed in 77 Dutch IPF patients and 349 healthy controls (HCs). CCL18 mRNA expression was analyzed in peripheral blood mononuclear cells (PBMCs) from 18 healthy subjects. Survival analysis was conducted, dependent on CCL18-levels and -genotypes and validated in two German IPF cohorts (Part B). IPF patients demonstrated significantly higher serum CCL18 levels than the healthy controls (p < 0.001). Both in IPF patients and HCs, serum CCL18 levels were influenced by rs2015086 C > T genotype, with the highest CCL18-levels with the presence of the C-allele. Constitutive CCL18 mRNA-expression in PBMCs was significantly increased with the C-allele and correlated with serum CCL18-levels. In IPF, high serum levels correlated with decreased survival (p = 0.02). Survival was worse with the CT-genotype compared to the TT genotype (p = 0.01). Concluding, genetic variability in the CCL18-gene accounts for differences in CCL18 mRNA-expression and serum-levels and influences survival in IPF.

Expression of CCL-18 and CX3CL1 in Serum, and Their Potential Roles as Two Diagnostic and Prognostic Markers in Chronic Obstructive Pulmonary Disease and Chronic cor Pulmonale (COPD&CCP): a Pilot Study.

CC chemokine ligand-18 (CCL-18) and CX3 chemokine ligand 1 (CX3CL1) are key factors of vascular and tissue injury in chronic respiratory diseases. Here, we investigated the value of CCL-18 and CX3CL1 in diagnosis and prognosis of patients with chronic obstructive pulmonary disease and chronic cor pulmonale (COPD&CCP). First, we investigated the expression profile of CCL-18 and CX3CL1 in serum of COPD&CCP patients. Then the relationship of the level of CCL-18 and CX3CL1 with clinicopathological characteristics was analyzed. Subsequently, we evaluated the diagnostic accuracy of CCL-18 and CX3CL1 to discriminate COPD&CCP. The prognostic value and therapy outcome were also evaluated. Compared to healthy subjects, the level of CCL-18 (8.01 ± 2.01 ng/mL) and CX3CL1 (2,096.11 ± 306.09 ng/mL) was significantly increased in COPD&CCP patients (p < 0.05). The upregulation of CCL-18 and CX3CL1 was significantly correlated with clinicopathological characteristics including CRP, IL-6, FIB, NT-proBNP, FEV1, FEV1/FVC, PASP, LVEF, and T wave anomaly. The combination of CCL-18 and CX3CL1 showed high precision for discriminating COPD&CCP with high AUC values (0.828), sensitivity (66.1%), and specificity (92.5%). Furthermore, CCL-18 and CX3CL1 acted as independent factors which lead to poor clinical benefits and indicated poor prognosis of COPD&CCP patients. Taken together, our results indicated that CCL-18 and CX3CL1 could act as suitable biomarkers in prognosis and prognostic evaluation of COPD&CCP.

The serum level of CC chemokine ligand 18 correlates with the prognosis of non-small cell lung cancer.

CC chemokine ligand 18 (CCL18) is a chemotactic cytokine involved in the pathogenesis and progression of various cancers. Our previous research showed that the expression of CCL18 is obviously higher in non-small cell lung cancer (NSCLC) than in the adjacent normal tissues, suggesting its role in NSCLC. We further examined the serum level of CCL18 in 80 NSCLC patients with enzyme-linked immunosorbent assay and simultaneously analyzed the survival curve of these patients by the Kaplan-Meier method, and then utilized a log-rank test to evaluate the correlation of CCL18 expression with the malignant progression of NSCLC. Our results showed that the median serum concentration of CCL18 was significantly elevated to 436.11 ng/mL in NSCLC patients compared to 41.97 ng/ml in healthy people (P<0.01), which was also positively related to the expression of lung cancer biomarkers carcinoma-embryonic antigen and cytokeratin fragment antigen 21-1. Moreover, correlation analysis showed that an increased level of serum CCL18 was associated with a worse survival time in NSCLC patients. Our findings suggest that the serum CCL18 level of NSCLC patients was negatively correlated with the prognosis, thus suggesting that CCL18 may serve as a potential circulating biomarker for NSCLC diagnosis.

MiR-128 targets the CC chemokine ligand 18 gene (CCL18) in cutaneous malignant melanoma progression

BackgroundThe CC chemokine ligand 18 (CCL18) has a higher expression in some tumors, while the CCL18 level can be a marker of tumor progression and prognosis. We previously reported that the expression of CCL18 gene was dramatically up-regulated in cutaneous malignant melanoma (CMM) and its expression levels were correlated with tumor thickness. ObjectiveTo investigate miRNAs which could target the CCL18 gene so as to mediate CMM development and improvement. MethodsThe expression of miR-128 and CCL18 in CMM were measured by qRT-PCR. The interaction of miR-128 with CCL18 3′UTR was verified by Luciferase reporter gene assay. The changes in expression of CCL18 after miR-128 mimic transfection of A375 melanoma cells were determined by both qRT-PCR and Western-bloting. Cell viability was accessed by CCK8-assay. Flow cytometry was employed to detect the incidence of apoptosis. Clonogenic assay was used to detect the ability of colony formation. Cell migration was evaluated by Transwell migration study. The protein levels of epithelial-mesenchymal transition (EMT), such as E-cadherin, N-cadherin and β-catenin were analyzed by Western-bloting. ResultsThe expression of miR-128 had negative relevance with CCL18 in CMM. miR-128 could interact with CCL18 3′UTR. Transfected miR-128 mimic significantly reduced CCL18 expression and this impairment of CCL18 gene promoted apoptosis, inhibited migration and colony formation of A375 melanoma cells. Furthermore, the relative expression of N-cadherin was decreased. ConclusionCCL18 is a target gene of miR-128. Overexpression of miR-128 inhibits the oncogenic effect of CCL18.

CC-Chemokine Ligand 18 Is an Independent Prognostic Marker in Lymph Node-positive Non-small Cell Lung Cancer.

Tumor-associated macrophages (TAMs) are key players in the immune response in non-small cell lung cancer (NSCLC) and the main producers of CC-chemokine ligand 18 (CCL18). Our study aimed to analyze the clinical significance of CCL18 expression by TAMs in NSCLC. Tissue multi-arrays from 243 non-selected patients with NSCLC were constructed. Immunohistochemical double staining for CD68 and CCL18 was performed and the number of CD68+, as well as CCL18+/CD68+ macrophages determined. Comparison of early to advanced lung adenocarcinoma showed significantly more frequent CD68+ as well as CD68/CCL18 double-positive macrophages in advanced disease (p=0.03 and p=0.04). Multivariate analysis revealed a higher proportion of double-positive macrophages to be an independent prognosticator in lymph node-positive NSCLC (hazard ratio(HR)=0.6, 95% confidence interval(CI)=0.35-0.86, p=0.009). In advanced lung adenocarcinoma, infiltration of CCL18+ TAMs was increased and higher expression of CCL18 by TAMs was associated with a favorable prognosis in lymph-node positive NSCLC.

Pirfenidone exerts a suppressive effect on CCL18 expression in U937-derived macrophages partly by inhibiting STAT6 phosphorylation

Context: CC chemokine ligand 18 (CCL18) is suggested to play a role in the development of pulmonary fibrosis. Macrophages are thought to be the main source of CCL18, and the effect of pirfenidone, an anti-fibrotic agent for idiopathic pulmonary fibrosis, on the expression of CCL18 in macrophages warrants investigation.Objective: The purpose of this study was to investigate the effect of pirfenidone on the expression of CCL18 in macrophages.Materials and methods: U937 cells were differentiated into macrophages by phorbol myristate acetate and then stimulated with recombinant IL-4 to induce the production of CCL18. The cells were treated with pirfenidone, and the mRNA and protein levels for CCL18 were measured by a reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The effects of pirfenidone on the IL-4 receptor (IL-4R) expression and STAT6 activation were investigated and on the JAK kinase activity were measured using the Z′-LYTE™ kinase assay.Results: Pirfenidone significantly suppressed the expression of CCL18 when the cells were treated with concentrations of 50–250 μg/mL. Pirfenidone did not affect the expression of the IL-4R components. The selective STAT6 inhibitor AS1517499 suppressed CCL18 expression. Both AS1517499 and pirfenidone suppressed STAT6 phosphorylation (p < .05), although the effect of pirfenidone was less marked than that of AS1517499. The Z′-LYTE™ kinase assay showed a reduction in the activities of JAK1, JAK3 and TYK2 by pirfenidone.Conclusion: Pirfenidone suppresses CCL18 expression in macrophages and this effect is thought to be attributed partly to the inhibition of STAT6 phosphorylation.

Expression of CC chemokine ligand 18 in cutaneous malignant melanoma tissues and its relationship with vascular endothelial growth factor and Ki67 antigen expressions

Objective To measure the expression of CC chemokine ligand 18 (CCL18) in cutaneous malignant melanoma (CMM) tissues, and to explore its clinical significance, as well as relationship with vascular endothelial growth factor (VEGF) and Ki67 antigen expressions. Methods Immunohistochemistry was performed to measure CCL18, VEGF and Ki67 expressions in 58 paraffin-embedded CMM tissue specimens, as well as CCL18 expression in 20 paraffin-embedded pigmented nevus specimens, and immunofluorescence assay to confirm the expression of CCL18 in fresh CMM tissue specimens. Correlations of CCL18 expression with CMM clinicopathologic features, VEGF and Ki67 expressions were analyzed. Results CCL18 was detected in 49 (84.48%) of 58 paraffin-embedded CMM specimens, but in none of the 20 paraffin-embedded pigmented nevus specimens, with a significant difference in the positive rate of CCL18 between the CMM group and pigmented nevus group (χ2 = 45.46, P 0.05). In addition, the expression of CCL18 in CMM tissues was positively correlated with that of VEGF (rs = 0.727, P 0.05). Immunofluorescence assay showed CCL18 expression in the cytoplasm of tumor cells in CMM tissues. Conclusion CCL18 is highly expressed in CMM tissues, and may be involved in tumor invasion and metastasis. Key words: Nevi and melanomas; Chemokine CCL18; Pathologic processes; Vascular endothelial growth factors; Ki-67 antigen

CC chemokine ligand 18(CCL18) promotes migration and invasion of lung cancer cells by binding to Nir1 through Nir1-ELMO1/DOC180 signaling pathway.

Non-small cell lung cancer (NSCLC) comprises nearly 80% of lung cancers and the poor prognosis is due to its high invasiveness and metastasis. CC chemokine ligand 18 (CCL18) is predominantly secreted by M2-tumor associated macrophages (TAMs) and promotes malignant behaviors of various human cancer types. In this study, we report that the high expression of CCL18 in TAMs of NSCLC tissues and increased expression of CCL18 in TAMs is correlated with the lymph node metastasis, distant metastasis, and poor prognosis NSCLC patients. CCL18 can increase the invasive ability of NSCLC cells by binding to its receptor Nir1. In addition, CCL18 is capable of modulating cell migration and invasion by regulating the activation of RAC1 which resulted in cytoskeleton reorganization in an ELMO1 dependent manner. Furthermore, we found that CCL18 could enhance adhesion of NSCLC cells via activating ELMO1-integrin β1 signaling. Thus, CCL18 and its downstream molecules may be used as targets to develop novel NSCLC therapy. © 2016 Wiley Periodicals, Inc.

Expression of CC-chemokine ligand 18 (CCL18) in the serum and pleural effusion of non-small-cell lung cancer patients and its regulatory effect on the differentiation of monocyte-derived dendritic cells

To compare the CC-chemokine ligand 18 (CCL18) expression in the serum and malignant pleural effusion (MPE) of NSCLC patients and explore its regulatory effect on differentiation of monocyte-derived dendritic cells (Mo-DC). CCL18 levels in the serum and MPE from 62 NSCLC patients were quantitated by immunoassay. CCL18 in sera from 26 healthy individuals, 28 exudative pleural effusions from inflammatory pulmonary diseases and 17 transudative pleural effusions from non-inflammatory diseases were used as control. Mo-DC was generated by culturing NSCLC-derived monocytes with GM-CSF and IL-4 in the presence or absence of CCL18. The mean fluorescent intensity (MFI) of CD14, CD80, CD83, CD86 and HLA-DR were analyzed by flow cytometry (FCM). Mo-DC was then co-cultured with purified T cells and the percence of CD25(+)FoxP3(+) cells was assayed by FCM. CCL18 levels in the sera of NSCLC patients and healthy individuals were (132.70 ± 15.52) ng/ml and (18.44 ± 0.99) ng/ml, respectively (P < 0.001). The levels of CCL18 in MPE, exudative PE and transudative PE were (155.6 ± 13.58) ng/ml, (190.4 ± 22.33) ng/ml and (20.89 ± 3.03) ng/ml, respectively. CCL18 in the MPE was significantly higher than that in transudates (P < 0.001), however, no significant difference was observed between CCL18 expression in exudative PE and MPE (P = 0.172). Of note, a moderate positive correlation (r = 0.421, P < 0.01) was observed between CCL18 levels in the paired MPE and serum of NSCLC. In the healthy control group, Mo-DC cultured in the presence of CCL18 showed 31.4 ± 15.8 (MFI) of CD14 expression, which was significantly higher than that in Mo-DC cultured in the absence of CCL18 (18.5 ± 8.9, P < 0.05). In contrast, the expressions of MFI of CD80, CD83, CD86 and HLA-DR were significantly decreased upon CCL18 induction (P < 0.05). In the NSCLC group, GM-CSF+IL-4+CCL18 induced a MFI of 45.2 ± 13.8 of CD14 expression in Mo-DC, which was also significantly higher than that of GM-CSF+ IL-4 induction (22.6 ± 10.5, P < 0.01). Similarly, the expressions of MFI of CD80, CD83, CD86 and HLA-DR were significantly decreased in the presence of CCL18 (P < 0.05). Furthermore, the MFI of CD14, CD83, CD86 and HLA-DR had significant differences between GM-CSF/IL-4/CCL18-induced Mo-DC derived from NSCLC patients and healthy control (P < 0.05). Finally, CD4(+) T cells co-cultured with NSCLC-derived, GM-CSF/IL-4/CCL18-treated Mo-DC had significantly higher percent of CD25(+)FoxP3(+) cells compared with that of CD4(+) T cells stimulated with Mo-DC induced by GM-CSF/IL-4(P < 0.01). CCL18 is present at a high level in MPE and serum of NSCLC patients complicated with pleural effusion and a moderate positive correlation exists between CCL18 levels in the two fluids. CCL18 inhibits maturation of Mo-DC, which consequently stimulates T cells to differentiate into CD25(+)FoxP3(+) regulatory T cells.

CC Chemokine Ligand 18 Correlates with Malignant Progression of Prostate Cancer

Background and Aim. CC chemokine ligand 18 (CCL18) promotes malignant behaviors of various human cancer types. However, its involvement in human prostate cancer has not been fully elucidated. The aim of this study was to investigate the role of CCL18 in PCa. Methods. Expression of CCL18 at mRNA and protein levels was detected using real-time qRT-PCR and immunohistochemistry analysis. We analyzed the associations of CCL18 expression with clinical features of human PCa. The effects of PCa cell migration, invasion, and apoptosis were tested. The efficiency of CCL18 on prostate tumor growth was assessed in a subcutaneous xenograft model. Results. CCL18 expression was upregulated (both P < 0.01) in PCa tissues compared with those in noncancerous prostate tissues. CCL18 upregulation was correlated with high Gleason score (P = 0.034) of patients with PCa. rCCL18 stimulation in PCa cells promoted cell migration and invasion but decreased DU145 cells apoptosis rate. Furthermore, subcutaneous homografts models showed the increased tumor growth and tumor vascularization with the CCL18 stimulation, and the expression of Ki67, PCNA, and CD31 in CCL18 stimulation mice was also significantly increased. Conclusions. Our data offer the convincing evidence that the upregulation of CCL18 may be involved in the malignant progression of PCa.

CCL18 Activates Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

To the Editor: Fibroblast-like synoviocytes (FLS) proliferate in the synovial tissue of patients with rheumatoid arthritis (RA), and contribute to chronic inflammation and the destruction of articular cartilage due to the production of a variety of cytokines, chemokines, and matrix metalloproteinases (MMP)1. The expression of CC chemokine ligand 18 (CCL18) was shown to be increased in the RA synovium2,3; however, the pathogenic role of CCL18 remains unclear. In this study, we investigated the expression of a recently identified receptor for CCL18, phosphatidylinositol transfer membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3)4 in the RA synovium, and the stimulatory effects of CCL18 on FLS. Synovial tissue samples were obtained from patients with RA (n = 4) and osteoarthritis (OA) (n = 4) undergoing joint replacement surgery. RA patients were a median 65 years old (range 48–85 yrs), with median disease duration 9 years (range 2.5–30 yrs) and median C-reactive protein level 1.23 mg/dl (range 0.68–2.85). All RA patients were positive for rheumatoid factor and anticitrullinated protein antibodies. All subjects provided informed consent. The experimental protocol was approved in advance by the Ethics Committee of Tokyo Medical and Dental University. CCL18-positive cells were observed in the synovial lining, sublining, and perivascular regions of the RA synovium (Figure 1A). CCL18 expression was minimal in the OA synovium (Figure 1C). Western blotting analysis showed that CCL18 expression was significantly higher in the RA synovium than in the OA synovium (Figure 1E, 1F). Double-immunofluorescence staining revealed that most CD68-positive macrophages expressed CCL18 (Figures 1G–1I), and von Willebrand factor (vWF)-positive vascular endothelial cells were also … Address correspondence to Dr. T. Nanki, Department of Medicine and Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail: nanki.rheu{at}tmd.ac.jp

Increased expression of CC chemokine ligand 18 in patients with chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with T(H)2-dominant inflammation, including eosinophilia, which is in contrast to chronic rhinosinusitis (CRS) without nasal polyps (NPs). CC chemokine ligand 18 (CCL18)/pulmonary and activation-regulated chemokine is known to recruit naive T cells, B cells, and immature dendritic cells, as well as to activate fibroblasts. CCL18 is thought to be involved in T(H)2-related inflammatory diseases, including asthma and atopic dermatitis. The objective of this study was to investigate the expression of CCL18 in patients with CRS. Using NP tissue and uncinate tissue (UT) from control subjects and patients with CRS, we examined the expression of CCL18 mRNA using real-time PCR and measured CCL18 protein using ELISA, Western blotting, and immunofluorescence. Compared with UT tissue from control subjects, CCL18 mRNA levels were significantly increased in NPs (P< .001) and UT (P< .05) from patients with CRSwNP but not in UT from patients with CRS without NPs. Similarly, CCL18 protein levels were increased in NPs and UT from patients with CRSwNP, and levels were even higher in patients with Samter's triad. Immunohistochemical analysis revealed CCL18 expression in inflammatory cells, and CCL18(+) cell numbers were significantly increased in NPs. Immunofluorescence data showed colocalization of CCL18 in CD68(+)/CD163(+)/macrophage mannose receptor-positive M2 macrophages and tryptase-positive mast cells in NPs. Levels of CCL18 correlated with markers of M2 macrophages but not with tryptase levels, suggesting that M2 macrophages are major CCL18-producing cells in NPs. Overproduction of CCL18 might contribute to the pathogenesis of CRSwNP through its known activities, which include recruitment of lymphocytes and dendritic cells, activation of fibroblasts, and initiation of local inflammation.

CCL18 Production is Decreased in Alveolar Macrophages from Cigarette Smokers

It is generally known that cigarette smoke alters the activation of alveolar macrophages (AM). CC Chemokine Ligand 18 (CCL18) is a marker of alternatively activated macrophages and is highly expressed in the lung. This study examines the influence of chronic cigarette smoking on the expression of CCL18 by AM. Bronchoalveolar lavage (BAL) and serum were obtained from ten smokers and 14 non-smokers. CCL18 protein concentrations were measured in serum and BAL fluid (BALF) as well as in supernatants from BAL-cells by enzyme-linked immunosorbent assay. In this study we show that the CCL18 production of BAL-cells from smokers was significantly decreased compared to BAL-cells from non-smokers. The BALF CCL18 protein concentration per macrophage cell count was significantly reduced in smokers. Furthermore, we show a decrease in CCL18 production from BAL-cells after stimulation with LPS. This decrease in CCL18 production was only shown in BAL-cells from non-smokers, which is probably due to chronic LPS exposure of smokers, resulting in LPS hypo-responsiveness. No statistically significant difference of CCL18 concentrations was found in BALF or serum of smokers versus non-smokers. CCL18 production by BAL-cells is down-regulated by chronic cigarette smoking and LPS contamination in cigarette smoke might be one factor involved. Thus this article gives further evidence that chronic cigarette smoking alters the phenotype of AM and that the M2 marker CCL18 is down-regulated in smokers macrophages.

Upregulation of CC chemokine ligand 18 and downregulation of CX3C chemokine receptor 1 expression in human T‐cell leukemia virus type 1‐associated lymph node lesions: Results of chemokine and chemokine receptor DNA chip analysis

Adult T-cell leukemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukemia virus type 1 (HTLV-1). The pathological features of the lymph nodes of ATLL change from those of lymphadenitis to Hodgkin's-like features and those of lymphoma. Chemokines and their receptors are closely associated with T-cell subgroups and immune responses. To clarify the relationship between chemokines and their receptor expression, as well as the development of ATLL, 17 cases with ATLL were analyzed using DNA chips of chemokines and their receptors. All cases showed a varied and mixed pattern of upregulated and downregulated gene expression of Th1, Th2, naïve, and cytotoxic cell-associated chemokine genes. As CC chemokine ligand 18 (CCL18) accounted for the most upregulated gene and CX3C chemokine receptor 1 (CX3CR1) for the most downregulated gene, they were selected for immunohistochemical analysis. Immunohistochemical staining showed expression of the two genes in immunological cells, with a positive expression for reticulum cells, but not for ATLL cells. HTLV-1-associated lymphadenitis type (n = 13) and Hodgkin's-like type (n = 12) cases showed significantly higher CCL18 expression than the non-specific lymphadenitis cases (n = 10) (P < 0.05). However, all HTLV-1-associated cases showed significantly lower CX3CR1 expression than the non-specific lymphadenitis cases (P < 0.05). These results suggest that upregulation of CCL18 expression and downregulation of CX3CR1 expression play a role in immune responses against the ATLL cells.

A Vicious Circle of Alveolar Macrophages and Fibroblasts Perpetuates Pulmonary Fibrosis via CCL18

Recently, models of macrophage activation have been revised. Macrophages stimulated with Th2 cytokines have been classified as alternatively activated. This article examines the expression and regulation of CC chemokine ligand 18 (CCL18), a marker of alternative activation, by human alveolar macrophages (AMs). AM were obtained from bronchoalveolar lavage (BAL) fluid of patients with idiopathic pulmonary fibrosis, sarcoidosis, or hypersensitivity pneumonitis (n = 69) and healthy volunteers (n = 22). Expression of CCL18 was determined by quantitative reverse transcriptase-polymerase chain reaction, in situ hybridization, flow cytometry, and immunohistochemistry, respectively. Spontaneous CCL18 production by BAL-derived cells was markedly increased in patients with pulmonary fibrosis and correlated negatively with pulmonary function test parameters. CCL18 gene expression and protein production were up-regulated in normal AMs after Th2 cytokine stimulation and/or coculture with human lung fibroblasts. Native collagen significantly up-regulated CCL18 expression in normal AMs activated with Th2 cytokines via a mechanism mediated by beta2-integrin/ scavenger receptor(s). Culture supernatants of AMs from patients with idiopathic pulmonary fibrosis increased collagen production by normal lung fibroblasts partly mediated via CCL18. Our findings suggest that AMs from patients with pulmonary fibrosis disclose a phenotype of alternative activation and might be a part of a positive feedback loop with lung fibroblasts perpetuating fibrotic processes.