Activated M2 Macrophages Contribute to the Pathogenesis of IgG4‐Related Disease via Toll‐like Receptor 7/Interleukin‐33 Signaling

Ishiguro, Nozomu; Moriyama, Masafumi; Furusho, Katsuhiro; Furukawa, Soichi; Shibata, Takuma; Murakami, Yusuke; Chinju, Akira; Haque, Absarul; Gion, Yuka; Ohta, Miho; Mitsui, Takashi; Tanaka, Akihiko; Yamauchi, Masaki; Sakamoto, M.; Mochizuki, Keita; Ono, Yuko; Hayashida, Jun Nosuke; Sato, Yasuharu; Kiyoshima, Tamotsu; Yamamoto, Hidetaka; Miyake, Kensuke; Nakamura, Seiji

doi:10.1002/art.41052

Cited by 57 publications

(58 citation statements)

References 51 publications

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“…In addition, the induction of remission by PSL markedly lowered the serum concentrations of IgG4, IFN-α, and IL-33. As has been shown in previous reports, including our own, the activation of IFN-α and IL-33 is involved in the immunopathogenesis of experimental AIP and human type 1 AIP/IgG4-RD 1 , 15 – 19 , 30 , 31 . However, the utility of serum IFN-α and IL-33 levels as biomarkers of type 1 AIP/IgG4-RD has never been evaluated.…”

Section: Discussionsupporting

confidence: 80%

Identification of serum IFN-α and IL-33 as novel biomarkers for type 1 autoimmune pancreatitis and IgG4-related disease

Minaga

Watanabe

Hara

et al. 2020

Sci Rep

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IgG4-related disease (IgG4-RD) is a multi-organ autoimmune disease characterized by elevated serum IgG4 concentration. Although serum IgG4 concentration is widely used as a biomarker for IgG4-RD and type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of IgG4-RD, a significant number of patients have normal serum IgG4 levels, even in the active phase of the disease. Recently, we reported that the development of experimental AIP and human type 1 AIP is associated with increased expression of IFN-α and IL-33 in the pancreas. In this study, we assessed the utility of serum IFN-α and IL-33 levels as biomarkers for type 1 AIP and IgG4-RD. Serum IFN-α and IL-33 concentrations in patients who met the diagnostic criteria for definite type 1 AIP and/or IgG4-RD were significantly higher than in those with chronic pancreatitis or in healthy controls. Strong correlations between serum IFN-α, IL-33, and IgG4 concentrations were observed. Diagnostic performance of serum IFN-α and IL-33 concentrations as markers of type 1 AIP and/or IgG4-RD was comparable to that of serum IgG4 concentration, as calculated by the receiver operating characteristic curve analysis. Induction of remission by prednisolone treatment markedly decreased the serum concentration of these cytokines. We conclude that serum IFN-α and IL-33 concentrations can be useful as biomarkers for type 1 AIP and IgG4-RD.

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Section: Discussionsupporting

confidence: 80%

Identification of serum IFN-α and IL-33 as novel biomarkers for type 1 autoimmune pancreatitis and IgG4-related disease

Minaga

Watanabe

Hara

et al. 2020

Sci Rep

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“…The binding leads to release of proinflammatory cytokines (IL-1 and IL-6), B cell growth factors (BAFF and APRIL) and Th2 differentiation cytokine (IL-4) to induce B cell maturation and Igs class-switch from IgE to IgG4 by modified Th2 response. For clarifying the properties of fibroinflammatory cytokines and their individual producing cells, many authors have successively demonstrated that IL-10 and IL-13 released from Th2, B lymphocyte-activating factor of TN F family (BAFF) and a proliferating inducing ligand (APRIL) released from M2-M φ and PMN, IL-4 and IRF-7 released from p DC, IL-33 released from antigen presenting cell (APC) and endothelial cell (EC) in patients with IgG4-RD [ 117 , 118 , 119 , 120 , 121 , 122 ]. In addition, activated M2-M φ may release profibrotic cytokines (TGF-β and IL-33) to activate the production of profibrotic cytokines from Treg including TGF-β, IL-10 and IL-33.…”

Section: The Cellular and Molecular Bases Of Allergy Inflammationmentioning

confidence: 99%

The Cellular and Molecular Bases of Allergy, Inflammation and Tissue Fibrosis in Patients with IgG4-related Disease

Hsieh

Shen

Liao

et al. 2020

IJMS

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IgG4-related disease (IgG4-RD) is a spectrum of complex fibroinflammatory disorder with protean manifestations mimicking malignant neoplasms, infectious or non-infectious inflammatory process. The histopathologic features of IgG4-RD include lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis together with increased in situ infiltration of IgG4 bearing-plasma cells which account for more than 40% of all IgG-producing B cells. IgG4-RD can also be diagnosed based on an elevated serum IgG4 level of more than 110 mg/dL (normal < 86.5 mg/mL in adult) in conjunction with protean clinical manifestations in various organs such as pancreato–hepatobiliary inflammation with/without salivary/lacrimal gland enlargement. In the present review, we briefly discuss the role of genetic predisposition, environmental factors and candidate autoantibodies in the pathogenesis of IgG4-RD. Then, we discuss in detail the immunological paradox of IgG4 antibody, the mechanism of modified Th2 response for IgG4 rather than IgE antibody production and the controversial issues in the allergic reactions of IgG4-RD. Finally, we extensively review the implications of different immune-related cells, cytokines/chemokines/growth factors and Toll-like as well as NOD-like receptors in the pathogenesis of tissue fibro-inflammatory reactions. Our proposals for the future investigations and prospective therapeutic strategies for IgG4-RD are shown in the last part.

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“…Indeed, effector T cell subpopulations, such as T helper type 2 cells, regulatory T cells and follicular helper T cells, are involved in the generation of IgG4 Ab responses [6]. In addition to the demonstration of the role of adaptive immune responses, studies have provided evidence that innate immunity also affects the development of AIP and IgG4-RD [12][13][14][15][16][17]. For example, the enhanced production of the innate immunity cytokines type I interferon (IFN) and interleukin (IL)-33 is a prominent feature of experimental AIP and human IgG4-RD [14,[16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Gut microbiome alterations in type 1 autoimmune pancreatitis after induction of remission by prednisolone

Kamata

Watanabe

Minaga

et al. 2020

Clinical and Experimental Immunology

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Although increasing evidence demonstrates the association between intestinal dysbiosis and pancreatic diseases such as chronic pancreatitis and pancreatic cancer, it remains largely unknown whether intestinal dysbiosis is involved in the immunopathogenesis of autoimmune pancreatitis (AIP). Recently, we found that intestinal dysbiosis mediates experimental AIP via the activation of plasmacytoid dendritic cells (pDCs), which can produce interferon (IFN)-α and interleukin (IL)-33. However, candidate intestinal bacteria, which promote the development of AIP, have not been identified. Fecal samples were obtained from type 1 AIP patients before and after prednisolone (PSL) treatment and subjected to 16S ribosomal RNA sequencing to evaluate the composition of intestinal bacteria. Induction of remission by PSL was associated with the complete disappearance of Klebsiella species from feces in two of the three analyzed patients with type 1 AIP. To assess the pathogenicity of Klebsiella species, mild experimental AIP was induced in MRL/MpJ mice by repeated injections of 10 μg of polyinosinic-polycytidylic acid [poly(I:C)], in combination with oral administration of heat-killed Klebsiella pneumoniae. The AIP pathology score was significantly higher in MRL/MpJ mice that received both oral administration of heat-killed K. pneumoniae and intraperitoneal injections of poly(I:C) than in those administered either agent alone. Pancreatic accumulation of pDCs capable of producing large amounts of IFN-α and IL-33 was also significantly higher in mice that received both treatments. These data suggest that intestinal colonization by K. pneumoniae may play an intensifying role in the development of type 1 AIP.

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Activated M2 Macrophages Contribute to the Pathogenesis of IgG4‐Related Disease via Toll‐like Receptor 7/Interleukin‐33 Signaling

Cited by 57 publications

References 51 publications

Identification of serum IFN-α and IL-33 as novel biomarkers for type 1 autoimmune pancreatitis and IgG4-related disease

Identification of serum IFN-α and IL-33 as novel biomarkers for type 1 autoimmune pancreatitis and IgG4-related disease

The Cellular and Molecular Bases of Allergy, Inflammation and Tissue Fibrosis in Patients with IgG4-related Disease

Gut microbiome alterations in type 1 autoimmune pancreatitis after induction of remission by prednisolone

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