Chemokine and chemokine receptors in autoimmunity: the case of primary biliary cholangitis

Choi, Jinjung; Selmi, Carlo; Leung, Patrick S.C.; Kenny, Thomas P.; Roskams, Tania; Gershwin, M. Eric

doi:10.1586/1744666x.2016.1147956

Cited by 49 publications

(40 citation statements)

References 159 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thence we compared the expression of chemokine receptors on MDSCs in IgG4-SC and HCs. We demonstrated that the expression of CCR2, CCR5, CCR6, CXCR3, and CX3CR1 (30)(31)(32)(33) on MDSCs was significantly increased in IgG4-SC compared to HCs (Fig. 3D; Supporting Fig.…”

Section: Rankl Induces Mdsc Expansion and Expression Of Ccr5 Cxcr3 mentioning

confidence: 87%

The Immunobiology of Receptor Activator for Nuclear Factor Kappa B Ligand and Myeloid‐Derived Suppressor Cell Activation in Immunoglobulin G4–Related Sclerosing Cholangitis

et al. 2018

Self Cite

View full text Add to dashboard Cite

The primary function of myeloid-derived suppressor cells (MDSCs) is reflected in their immune modulatory role in several immune-mediated diseases. In immunoglobulin G4 (IgG4)-related disease (IgG4-RD), it has been hypothesized that there are selective regulatory defects that lead to a T helper 2 (Th2) bias immune response. Herein we have taken advantage of a large cohort of patients with IgG4-related sclerosing cholangitis (IgG4-SC), the most common extrapancreatic involvement of IgG4-RD, as well as controls consisting of primary sclerosing cholangitis, autoimmune hepatitis, and healthy volunteers, to study MDSCs. We report dramatically increased levels of receptor activator for nuclear factor kappa B ligand (RANKL) expression in serum and liver from patients with IgG4-SC compared to both liver-disease and healthy controls. Moreover, in IgG4-SC liver, RANKL-secreting cells specifically colocalized with cluster of differentiation 38-positive plasma cells and MDSCs, particularly monocytic MDSCs, and express the RANKL receptor in liver. Similarly, the frequency and number of peripheral blood MDSCs were significantly increased. Importantly, serum expression levels of RANKL were inversely correlated with the serum level of gamma-glutamyltransferase but significantly positively correlated with the frequency of MDSCs. Moreover, we confirmed that RANKL induced the expansion and activation of MDSCs through the RANKL/RANK/nuclear factor kappa B signal pathway. Of note, RANKL-treated MDSCs suppressed T-cell proliferation and induced Th2 differentiation. Conclusion: Our data suggest that plasma cell-derived RANKL induces the expansion and activation of MDSCs, which suppress T-cell proliferation and contribute to the Th2-type response characteristic of IgG4-SC.

show abstract

Section: Rankl Induces Mdsc Expansion and Expression Of Ccr5 Cxcr3 mentioning

confidence: 87%

The Immunobiology of Receptor Activator for Nuclear Factor Kappa B Ligand and Myeloid‐Derived Suppressor Cell Activation in Immunoglobulin G4–Related Sclerosing Cholangitis

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…The interaction of CX 3 CL1 and its receptor CX 3 CR1 contributes to the recruitment of various immune cells including T cells, monocytes and NK cells causing inflammatory autoimmune diseases such as RA and SLE. [96][97][98][99] Moreover, stimulation by CX 3 CL1 was found to trigger the proliferation of fibroblasts and atherosclerosis as well as leading to an increased MMPs and further inflammation in RA joints. [100][101][102][103][104] Multiple studies in RA have been carried out with antagonists and/or neutralizing antibodies against chemokines including CCR1, CCR5, CXCR4, CXCR7, CCL19, CXCL10, CXCL12, and CXCL13, where they revealed potential to be future targets.…”

Section: Chemokines In Rheumatoid Arthritismentioning

confidence: 99%

<p>Role of Chemokines and Chemokine Receptors in Rheumatoid Arthritis</p>

Elemam¹,

Hannawi

Maghazachi³

2020

ITT

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases and a prototypic inflammatory disease, affecting the small joints of the hands and feet. Chemokines and chemokine receptors play a critical role in RA pathogenesis via immune cells recruitment. Several chemokines and chemokine receptors are abundant in the peripheral blood and in the local inflamed joints of RA. Furthermore, synthetic and biologics disease modifying anti rheumatic drugs have been reported to affect chemokines expression. Thus, many studies have focused on targeting chemokines and chemokine receptors, where some have shown positive promising results. However, most of the chemokine blockers in human trials of RA treatment displayed some failures that can be attributed to several reasons in their structures and binding affinities. Nevertheless, targeting chemokines will continue to be under development, in order to improve their therapeutic potentials in RA and other autoimmune diseases. In this review we provide an up-to-date knowledge regarding the role of chemokines and chemokine receptors in RA with an emphasis on their activities on immune cells. We also discussed the effects of drugs targeting those molecules in RA. This knowledge might provide impetus for developing new therapeutic modalities to treat this chronic disease.

show abstract

“…Recently, obeticholic acid, a selective ligand of the farnesoid X receptor, was approved for patients who are refractory to UDCA . However, the efficacy of obeticholic acid is still suboptimal, and additional therapeutic approaches are urgently needed …”

Section: Introductionmentioning

confidence: 99%

Toward solving the etiological mystery of primary biliary cholangitis

Tanaka

Leung

Young

et al. 2017

Hepatology Communications

Self Cite

View full text Add to dashboard Cite

Primary biliary cholangitis (PBC) is considered a model autoimmune disease due to its signature anti‐mitochondrial antibody (AMA) autoantibody, female predominance, and relatively specific portal infiltration and cholestasis. The identification and cloning of the major mitochondrial autoantigens recognized by AMA have served as an immunologic platform to identify the earliest events involved in loss of tolerance. Despite the relatively high concordance rate in identical twins, genome‐wide association studies have not proven clinically useful and have led to suggestions of epigenetic events. To understand the natural history and etiology of PBC, several murine models have been developed, including spontaneous models, models induced by chemical xenobiotic immunization, and by “designer” mice with altered interferon metabolism. Herein, we describe five such models, including 1) NOD.c3c4 mice, 2) dominant negative form of transforming growth factor receptor type II mice, 3) interleukin‐2R α−/− mice, 4) adenylate‐uridylate‐rich element Del−/− mice, and 5) 2‐octynoic acid‐conjugated bovine serum albumin immunized mice. Individually there is no perfect murine model, but collectively the models point to loss of tolerance to PDC‐E2, the major mitochondrial autoantigen, as the earliest event that occurs before clinical disease is manifest. Although there is no direct association of AMA titer and PBC disease progression, it is noteworthy that the triad of PBC monocytes, biliary apotopes, and AMA leads to an intense proinflammatory cytokine burst. Further, the recurrence of PBC after liver transplantation indicates that, due to major histocompatibility complex restriction, disease activity must include not only adaptive immunity but also innate immune mechanisms. We postulate that successful treatment of PBC may require a personalized approach with therapies designed for different stages of disease. (Hepatology Communications 2017;1:275–287)

show abstract

Chemokine and chemokine receptors in autoimmunity: the case of primary biliary cholangitis

Cited by 49 publications

References 159 publications

The Immunobiology of Receptor Activator for Nuclear Factor Kappa B Ligand and Myeloid‐Derived Suppressor Cell Activation in Immunoglobulin G4–Related Sclerosing Cholangitis

The Immunobiology of Receptor Activator for Nuclear Factor Kappa B Ligand and Myeloid‐Derived Suppressor Cell Activation in Immunoglobulin G4–Related Sclerosing Cholangitis

<p>Role of Chemokines and Chemokine Receptors in Rheumatoid Arthritis</p>

Toward solving the etiological mystery of primary biliary cholangitis

Contact Info

Product

Resources

About