The multifaceted role of mast cells in joint inflammation and arthritis

Loucks, Abigail; Maerz, Tristan; Hankenson, Kurt D.; Moeser, Adam J.; Colbath, Aimée C.

doi:10.1016/j.joca.2023.01.005

Cited by 14 publications

(11 citation statements)

References 84 publications

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“…In a mouse model of MCTD, IgE deficiency fully prevented the development of the associated lung disease 38 . In RA, increased blood IgE levels, prevalence of anti‐nuclear IgE (49%), and IgE‐containing immune complexes in synovial fluid are associated with disease activity, as is the activation of mast cells in synovium 15,39 . Whether the latter is FcεRI‐ and/or IgE‐mediated still needs to be investigated 39 …”

Section: Autoreactive Ige In Systemic Lupus Erythematosus and Other A...mentioning

confidence: 99%

“…38 In RA, increased blood IgE levels, prevalence of anti-nuclear IgE (49%), and IgE-containing immune complexes in synovial fluid are associated with disease activity, as is the activation of mast cells in synovium. 15,39 Whether the latter is FcεRI-and/or IgE-mediated still needs to be investigated. 39 As indicated in Table 1, the prevalence of IgE AAb in other autoimmune connective tissue diseases suggests that they may have a pathogenic role in these conditions (Table 1).…”

Section: Autore Ac Tive I G E In Sys Temi C Lupus Ery Thematosus and ...mentioning

confidence: 99%

“…15,39 Whether the latter is FcεRI-and/or IgE-mediated still needs to be investigated. 39 As indicated in Table 1, the prevalence of IgE AAb in other autoimmune connective tissue diseases suggests that they may have a pathogenic role in these conditions (Table 1). Indeed, several FcεRIbearing cells are involved in the pathogenesis of these conditions (for instance: mast cells in RA and SSc; pDC in RA, GS, and SSc).…”

Section: Autore Ac Tive I G E In Sys Temi C Lupus Ery Thematosus and ...mentioning

confidence: 99%

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Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases

Charles

Krohn

Kocatürk

et al. 2023

Allergy

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Autoimmunity is the break of tolerance to self‐antigens that leads to organ‐specific or systemic diseases often characterized by the presence of pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or plasma cells. AAb are prevalent in the general population and not systematically associated with clinical symptoms. In contrast, in some individuals, these AAb are pathogenic and drive the development of signs and symptoms of antibody‐mediated autoimmune diseases (AbAID). AAb production, isotype profiles, and glycosylations are promoted by pro‐inflammatory triggers linked to genetic, environmental, and hormonal parameters. Recent evidence supports a role for pathogenic AAb of the IgE isotype in a number of AbAID. Autoreactive IgE can drive the activation of mast cells, basophils, and other types of FcεRI‐bearing cells and may play a role in promoting autoantibody production and other pro‐inflammatory pathways. In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID.

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Section: Autoreactive Ige In Systemic Lupus Erythematosus and Other A...mentioning

confidence: 99%

Section: Autore Ac Tive I G E In Sys Temi C Lupus Ery Thematosus and ...mentioning

confidence: 99%

Section: Autore Ac Tive I G E In Sys Temi C Lupus Ery Thematosus and ...mentioning

confidence: 99%

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Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases

Charles

Krohn

Kocatürk

et al. 2023

Allergy

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show abstract

“…In a mouse model of MCTD, IgE deficiency fully prevented the development of the associated lung disease 38 . In RA, increased blood IgE levels, prevalence of anti-nuclear IgE (49%), and IgE-containing immune complexes in synovial fluid are associated with disease activity, as is the activation of mast cells in synovium 15,39 . Whether the latter is FcεRI-and/or IgE-mediated still needs to be investigated 39 .…”

Section: Introductionmentioning

confidence: 99%

Autoreactive IgE: pathogenic role and therapeutic target in autoimmune diseases

Charles

Krohn

Kocatürk

et al. 2023

Preprint

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Autoimmunity is the break of tolerance to self-antigens that leads to organ-specific or systemic diseases characterized by the presence of pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or plasma cells. AAb are prevalent in the general population and not systematically associated with clinical symptoms. In contrast, in some individuals, these AAb are pathogenic and drive the development of signs and symptoms of antibody-mediated autoimmune diseases (AbAID). AAb production, isotype profiles, and glycosylations are promoted by pro-inflammatory triggers linked to genetic, environmental, and hormonal parameters. Recent evidence supports a role for pathogenic AAb of the IgE isotype in a number of AbAID. Autoreactive IgE can drive the activation of mast cells, basophils and other types of FcεRI-bearing cells and may play a role in promoting autoantibody production and other pro-inflammatory pathways. In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID.

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“…Activation of phagocytes is followed by the release of reactive oxygen species and degrading enzymes, which lead to tissue damage ( 20 ), while osteoclasts are responsible for bone resorption ( 21 ). Mast cells and platelet-derived microvesicles are also involved in the development of arthritis by releasing proinflammatory cytokines ( 22 , 23 ). Although hematopoietic cells are key elements of tissue damage in arthritic conditions, fibroblast-like synoviocytes are also essential for the development of the disease ( 24 , 25 ).…”

Section: Introductionmentioning

confidence: 99%

Lacking ARHGAP25 mitigates the symptoms of autoantibody-induced arthritis in mice

et al. 2023

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ObjectiveDespite intensive research on rheumatoid arthritis, the pathomechanism of the disease is still not fully understood and the treatment has not been completely resolved. Previously we demonstrated that the GTPase-activating protein, ARHGAP25 has a crucial role in the regulation of basic phagocyte functions. Here we investigate the role of ARHGAP25 in the complex inflammatory process of autoantibody-induced arthritis.MethodsWild-type and ARHGAP25 deficient (KO) mice on a C57BL/6 background, as well as bone marrow chimeric mice, were treated i.p. with the K/BxN arthritogenic or control serum, and the severity of inflammation and pain-related behavior was measured. Histology was prepared, leukocyte infiltration, cytokine production, myeloperoxidase activity, and superoxide production were determined, and comprehensive western blot analysis was conducted.ResultsIn the absence of ARHGAP25, the severity of inflammation, joint destruction, and mechanical hyperalgesia significantly decreased, similarly to phagocyte infiltration, IL-1β, and MIP-2 levels in the tibiotarsal joint, whereas superoxide production or myeloperoxidase activity was unchanged. We observed a significantly mitigated phenotype in KO bone marrow chimeras as well. In addition, fibroblast-like synoviocytes showed comparable expression of ARHGAP25 to neutrophils. Significantly reduced ERK1/2, MAPK, and I-κB protein signals were detected in the arthritic KO mouse ankles.ConclusionOur findings suggest that ARHGAP25 has a key role in the pathomechanism of autoantibody-induced arthritis in which it regulates inflammation via the I-κB/NF-κB/IL-1β axis with the involvement of both immune cells and fibroblast-like synoviocytes.

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The multifaceted role of mast cells in joint inflammation and arthritis

Cited by 14 publications

References 84 publications

Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases

Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases

Autoreactive IgE: pathogenic role and therapeutic target in autoimmune diseases

Lacking ARHGAP25 mitigates the symptoms of autoantibody-induced arthritis in mice

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