China
Africa
Explore chapters and articles related to this topic
Role of dendritic cells in integrating immune responses to luminal antigens
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Brian L. Kelsall, Maria Rescigno
DCs that have captured antigens undergo a process of maturation, either constitutively through unclear mechanisms that may involve changes in homeotypic adhesion or through activation by pattern-recognition receptors (PRRs) or inflammatory cytokines (interleukin [IL]-1α/β, tumor necrosis factor [TNF]-α), resulting in increased maturation and migration. DC maturation is characterized by a decreased capacity to take up antigen (to prevent processing of additional self-antigens), increased processing of antigen into MHC I and II and peptide complexes, and expression of costimulatory molecules. Expression of MHC peptide complexes and costimulatory molecules is markedly increased on the expanded cell surface that results from formation of extended dendritic processes. This maturation process coincides with DC migration from nonlymphoid tissues or from the marginal zones to T-cell zones of draining lymph nodes due to expression of CCR7, which allows DCs to enter lymphatics. cDCs localize along connective tissue fibers and present the antigen to circulating naïve T cells attracted by chemokines such as DC-derived CCL18. In addition, mature DCs express adhesion molecules, including LFA-1 (CD11a/CD18), LFA-3 (CD58), and DC-SIGN (CD209). DC-SIGN binds transiently and with high avidity to ligands expressed by naïve T cells, thereby enhancing T-cell sampling of DC-expressed MHC–peptide complexes. LFA-1 and LFA-3 expressed on mature DCs bind naïve T-cell ICAM-3 and CD2, respectively, promoting T-cell activation.
Phagocytic cells and their functions
Published in Gabriel Virella, Medical Immunology, 2019
Gabriel Virella, John W. Sleasman
Macrophages can be separated into three populations: M0, M1, and M2. M0 macrophages are resting cells, able to ingest by phagocytosis or endocytosis, while M1 and M2 are activated macrophage populations. In humans, M1 macrophages, also known as classically activated macrophages, do not endocytose. Two main activation stimuli have been used: LPS and interferon γ (IFNγ). Once activated, they express CD64, and when LPS is added to IFNγ or used by itself, the M1 macrophages also express CD80. M1 macrophages are proinflammatory and express CCL17 and CCL18, but they release different cytokines depending on how they are activated. IFNγ activation induces the release of additional IFNγ, while LPS-activated M1 release very small amounts of IFNγ and predominantly release TNF, IL-1β, RANTES, IL-8, and other proinflammatory cytokines, closer to what is observed when human macrophages are activated via the Fcγ receptors. Activation with IFNγ suppresses the expression of cell recruitment genes activated by LPS, thus suggesting that it can also contribute to the resolution of an inflammatory reaction.
Lung transplantation for ILD
Published in Muhunthan Thillai, David R Moller, Keith C Meyer, Clinical Handbook of Interstitial Lung Disease, 2017
A number of studies have attempted to address the factors that could predict disease progression in IPF. Serological tests that may act as surrogate markers include surfactant protein D (SP-D), KL-6, LDH and erythrocyte sedimentation rate (ESR) (7). Limited data suggest that KL-6 may predict response to treatment in the rapidly progressive IPF group (8). Prasse et al. suggested that elevated levels of CCL18 predict change in forced vital capacity (FVC) and total lung capacity (TLC) at 6 months (9). Interestingly, SP-D levels decrease following bilateral lung transplant (BLT) but remain elevated after single lung transplant (SLT), perhaps indicating that in some individuals this biomarker may be useful (10). Hypoalbuminaemia at the time of transplantation has also been shown to be an independent risk factor for mortality in an analysis of United Network for Organ Sharing (UNOS) data (11). However, despite these promising studies no single biomarker has yet been universally adopted for lung transplantation assessment.
Epithelial–mesenchymal Transition of Peritoneal Mesothelial Cells Is Enhanced by M2c Macrophage Polarization
Published in Immunological Investigations, 2022
Lifang Tian, Qiaoling Yu, Dan Liu, Zhao Chen, Yuzhan Zhang, Jiamei Lu, Xiaoqin Ma, Fumeng Huang, Jin Han, Lingting Wei, Lei Zhang, Jie Gao, Li Wang, Rongguo Fu
We had thought that TGF-β1 should be the main mediator secreted by M2c to influence EMT of PMCs. Unexpectedly the results were contrary to our original guessing. The level of TGF-β1 release by M2c macrophages was lower. Reportedly IL-10 can promote fibrosis in some context (Beretta et al. 2007; Carrington et al. 2006; Le et al. 1997; van den Berg 1998). Thus, IL-10 should be another pathway. Our results prove that the amount of IL-10 secreted by M2c macrophages was much more than that by other subsets. Previous studies proved that the degradation degree of peritoneal function was positively correlated with the expression of CCL18 in peritoneal dialysis fluid (Bellon et al. 2011; Mantovani et al. 2004; Wynn et al. 2013). CCL18 is primarily responsible for the recruitment of adaptive immune system (Adema et al. 1997; Chenivesse et al. 2012; Nadaï et al. 2006; Vulcano et al. 2003). Thus, we surmise CCL18 could be one pathway too. Of course, it needs further verification.
Biomarkers of skin and lung fibrosis in systemic sclerosis
Published in Expert Review of Clinical Immunology, 2019
Dušanka Martinović Kaliterna, Marin Petrić
Chemokine (C-C motif) ligand 18 (CCL18) is a small chemotactic cytokine produced by antigen-presenting cells, particularly by alveolar macrophages. It has plenty of functions, but one of the most significant is the activation of the adaptive immune system. Primarily, it was named as pulmonary and activation-regulated chemokine, as well as dendritic cell-cytokine 1 [100,101]. CCL18 is increased in serum, bronchoalveolar lavage (BAL) fluid and alveolar macrophage culture in various inflammatory and fibrotic ILD, including SSc, and its concentrations reflect pulmonary fibrotic activity, as shown by two independent prospective and cross-sectional studies [102,103]. A Japanese study found a negative correlation between serum CCL18 levels, and DLCO and FVC in SSc. This study also established that serum CCL18 levels were significantly decreased in SSc patients with an inactive pulmonary fibrosis, compared to those with active fibrosis, making it a rather sensitive, though unspecific biomarker [104]. Growth/differentiation factor 15 (GDF15), part of the TGF-β superfamily, is a cytokine that is commonly related to the regulation of inflammatory pathways [105]. Yanaba et al. showed its clinical significance in the early phases of cutaneous and pulmonary fibrosis in SSc, although during follow up its concentrations were generally decreased [106]. Lambrecht et al. [107] also confirmed similar findings in mice model and showed that GDF-15 was involved, but not indispensable, in fibrosis development, making it an unsuitable marker for disease monitoring.
The fibrogenic chemokine CCL18 is associated with disease severity in Erdheim-Chester disease
Published in OncoImmunology, 2018
Greta Pacini, Giulio Cavalli, Alessandro Tomelleri, Giacomo De Luca, Guido Pacini, Marina Ferrarini, Claudio Doglioni, Lorenzo Dagna
This study points at the involvement of the pro-fibrotic mediator CCL18 in the pathogenesis of fibrosis that characterizes ECD. CCL18 is produced by macrophages and mainly involved in orchestrating cell-migration and homing.9 Of note, CCL18 expression is induced by Th2-related cytokines,9,10 thus representing a marker for macrophages non-canonically activated by Th2-related stimuli, termed ‘alternatively activated’ macrophages. CCL18 and alternatively activated macrophages are known to stimulate collagen production and fibroblast proliferation, in part through the activation of the MAPK pathway.11,12 In this study, circulating levels of CCL18 were strikingly elevated in ECD patients compared to controls (p < 0.001). Interestingly, this elevation was independent of treatment status, a finding consonant with clinical observations that fibrosis in ECD is poorly responsive to available therapies. In ECD lesions, we observed a marked expression of CCL18 with a prominent localization within infiltrating foamy histiocytes, a finding suggesting that this potent chemo-attractant may also be involved in lymphocyte and macrophage recruitment into ECD lesions. Indeed, elevated levels of CCL18 are encountered in several other diseases characterized by both leucocyte recruitment and fibrosis, including pulmonary fibrosis, systemic sclerosis, and Gaucher disease.13-15