Langerhans cell histiocytosis: a cytokine/chemokine-mediated disorder?

Garabedian, Lara; Struyf, Sofie; Opdenakker, Ghislain; Sozzani, Silvano; Damme, Jozef Van; Laureys, Geneviève

doi:10.1684/ecn.2011.0290

Cited by 23 publications

(20 citation statements)

References 41 publications

(62 reference statements)

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“…D,E) . Furthermore, we measured cytokine levels of IL‐1a, IL‐7, IL‐17, TNF‐α, and IFN‐γ, which have previously been shown to be up‐regulated in LCH lesions . The most abundant cytokine was IFN‐γ, followed by TNF‐α.…”

Section: Resultsmentioning

confidence: 98%

JAG2 signaling induces differentiation of CD14+ monocytes into Langerhans cell histiocytosis-like cells

Schwentner

Jug

Kauer

et al. 2018

Journal of Leukocyte Biology

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Langerhans cell histiocytosis (LCH) is a MAPK pathway-driven disease characterized by the accumulation of CD1a + langerin + cells of unknown origin. We have previously reported that the Notch signaling pathway is active in LCH lesions and that the Notch ligand Jagged2 (JAG2) induces CD1a and langerin expression in monocytes in vitro. Here we show that Notch signaling induces monocytes to acquire an LCH gene signature and that Notch inhibition suppresses the LCH phenotype.In contrast, while also CD1c + dendritic cells or IL-4-stimulated CD14 + monocytes acquire CD1a and langerin positivity in culture, their gene expression profiles and surface phenotypes are more different from primary LCH cells. We propose a model where CD14 + monocytes serve as LCH cell precursor and JAG2-mediated activation of the Notch signaling pathway initiates a differentiation of monocytes toward LCH cells in selected niches and thereby contributes to LCH pathogenesis. K E Y W O R D SBRAFV600E, notch pathway, pediatric neoplasm BRAFV600E mutation alone is not instructive for a cell to develop an LCH phenotype.We have previously shown that the Notch pathway is active in LCH and that stimulation of the Notch pathway in the presence of

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Section: Resultsmentioning

confidence: 98%

JAG2 signaling induces differentiation of CD14+ monocytes into Langerhans cell histiocytosis-like cells

Schwentner

Jug

Kauer

et al. 2018

Journal of Leukocyte Biology

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“…Interactions among cytokines, chemokines, and immune cells are dynamic processes (14). Certain cytokines and chemokines could recruit and active immune cells, including T cells, B cells, monocytes, neutrophils, and other type of cells from peripheral blood to the liver in HBV infection (12, 15).…”

Section: Discussionmentioning

confidence: 99%

Expression Profiles of Circulating Cytokines, Chemokines, and Immune Cells in Patients With Hepatitis B Virus Infection

et al. 2014

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Background:Immune cells and molecules play a vital role in initiating, maintaining, regulating immunological homeostasis and inflammation in many pathological and physiological processes; however, the changes on expressions and functions of these cells and molecules in hepatitis B virus (HBV) infection have not been elucidated well.Objectives:The current study aimed to determine the expression pattern of different cytokines, chemokines, immune cells in HBV infection and their association with disease progression.Patients and Methods:Sixty-nine patients with chronic HBV infection were enrolled. Five immune cell subsets and 46 cytokines and chemokines were analyzed by flow cytometry and Luminex 200.Results:In comparison to healthy individuals and asymptomatic HBV carriers, expression of CXCL9, CXCL10, CXCL11, and IL-10 were elevated in patients with chronic active HBV and had positive correlation with ALT levels. In contrast, G-CSF, MCP-3, and IFN-γ levels were significantly decreased in patients with chronic active HBV infection in contrast to carriers and healthy individuals; however, these down regulations did not show any correlation with either virological findings or liver inflammation. Although the proportion of CD4+ CD25 high regulatory T cells (Tregs) was higher in patients with HBV infection than in healthy controls, no correlations were found between Tregs and other cytokines or chemokines.Conclusions:CXCR3-associated chemokines might contribute to liver inflammation in chronic hepatitis B, while MCP-3 and G-CSF were inhibited by HBV infection. Host immune response was suppressed as manifested by an increase in CD4+ CD25high Tregs and IL-10 as well as a decrease in IFN-γ. Exploiting the expression pattern of cytokine and chemokine may help to develop a better understanding of chronic HBV infection pathogenesis.

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“…Certain inflammatory chemokines activate immune cells to initiate an immune response or promote wound healing [10]; they are released by many different cell types and activate cells of both the innate and adaptive immune system. Interactions between cytokines/chemokines and the cellular immune system is a dynamic process [11]. The interactions of positive and negative stimuli, as well as positive and negative regulatory loops are complex and often involve multiple cytokines.…”

Section: Introductionmentioning

confidence: 99%

Expression Pattern of Serum Cytokines in Hepatitis B Virus Infected Patients with Persistently Normal Alanine Aminotransferase Levels

Guo

et al. 2013

J Clin Immunol

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PurposeAbout 60–80 % of chronic hepatitis B virus (HBV) carriers are characterized with persistently normal alanine transaminase (ALT). Differences of cytokine expression are associated with the prognosis of HBV infection. We investigated the expression pattern of 30 cytokines associated with anti-HBV immunity in patients with normal ALT.MethodsFour patient groups (immune tolerance, inactive hepatitis B surface antigen carriers, resolved hepatitis B, and control; 10 subjects per group) were assigned. Thirty cytokines, including IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-17C, IL-21, IL-22, IL-23p19, IL-28A, IL-29, CCL5, CCL16, CCL20, CCL22, CXCL9, CXCL10, CXCL11, TNFRSF8, TNFRSF18, IL-6R, gp130, and TGF-β1, were measured using a human cytokine antibody array. Signal intensities were obtained by laser scanner. Protein-protein interactions were analyzed by STRING (Search Tool for the Retrieval of Interacting Genes/Proteins).ResultsSignificant differences of signal intensities were observed for IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12p40, IL-12p70, IL-15, IL-21, IL-23p19, IL-28A, and IL-29. The lowest intensity was in controls. Among three HBV infection groups, significant differences were observed in IL-2, IL-4, IL-12p70, IL-15, IL-21, IL-23p19, and IL-29. The highest intensity was in the inactive group. All cytokines with significant differences were involved JAK-STAT signaling that up-regulate FOXP3, SOCS3 and MX1.ConclusionDifferential expression of cytokines in JAK-STAT signaling is an important factor associated with prognosis of HBV infection. The elevation of γC cytokines, IL-12p70, IL-23p19, and IL-29 may promote spontaneous HBeAg seroconversion and HBV clearance.Electronic supplementary materialThe online version of this article (doi:10.1007/s10875-013-9931-0) contains supplementary material, which is available to authorized users.

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Langerhans cell histiocytosis: a cytokine/chemokine-mediated disorder?

Cited by 23 publications

References 41 publications

JAG2 signaling induces differentiation of CD14+ monocytes into Langerhans cell histiocytosis-like cells

JAG2 signaling induces differentiation of CD14+ monocytes into Langerhans cell histiocytosis-like cells

Expression Profiles of Circulating Cytokines, Chemokines, and Immune Cells in Patients With Hepatitis B Virus Infection

Expression Pattern of Serum Cytokines in Hepatitis B Virus Infected Patients with Persistently Normal Alanine Aminotransferase Levels

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