Transgenic mice expressing human FcγRIIa have enhanced sensitivity to induced autoimmune arthritis as well as elevated Th17 cells

Velde, Nicholas C. van de; Mottram, Patricia L.; Powell, Maree S.; Lim, Bryan; Holmdahl, Rikard; Hogarth, P. Mark

doi:10.1016/j.imlet.2009.12.005

Cited by 23 publications

(15 citation statements)

References 49 publications

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“…In humans, hFcγRIIA, and more particularly, hFcγRIIA-R131, is associated with RA development (15). However, as mice do not express hFcγRIIA, the transgenic expression of hFcγRIIA was established to develop a mouse model relevant to the human RA disease (37). We confirm here that transgenic mice expressing hFcγRIIA alone on a FcRγ -/-background were prone to developing arthritis.…”

Section: Discussionsupporting

confidence: 67%

Shifting FcγRIIA-ITAM from activation to inhibitory configuration ameliorates arthritis

Mkaddem¹,

Hayem²,

Jönsson³

et al. 2014

J. Clin. Invest.

114

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Section: Discussionsupporting

confidence: 67%

Shifting FcγRIIA-ITAM from activation to inhibitory configuration ameliorates arthritis

Mkaddem¹,

Hayem²,

Jönsson³

et al. 2014

J. Clin. Invest.

114

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“…To test this, we performed the CIA model in female C57BL/6 mice, which are resistant in this particular experimental model of arthritis in mice overexpressing IL-17A or GFP[33]. IL-17A exacerbated the disease progression compared to GFP controls, and showed a strong upregulation of RANKL, TRAP and MMP9 mRNA, correlating with the osteoclast-related gene activation signature.…”

Section: Discussionmentioning

confidence: 99%

IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis

et al. 2014

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Background Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by clinical features that include bone loss and epidermal hyperplasia. Aberrant cytokine expression has been linked to joint and skin pathology; however, it is unclear which cytokines are critical for disease initiation. IL-17A participates in many pathologic immune responses; however, its role in PsA has not been fully elucidated. Objective To determine the role of IL-17A in epidermal hyperplasia and bone destruction associated with psoriatic arthritis. Design An in vivo gene transfer approach was used to investigate the role of IL-17A in animal models of inflammatory (Collagen-induced arthritis) and non-inflammatory (RANKL-gene transfer) bone loss. Results IL-17A gene transfer induced the expansion of IL-17RA+CD11b+Gr1low osteoclast precursors and a concomitant elevation of biomarkers indicative of bone resorption. This occurred at a time preceding noticeable joint inflammation suggesting that IL-17A is critical for the induction of pathological bone resorption through direct activation of osteoclast precursors. Moreover, IL-17A induced a second myeloid population CD11b+Gr1high neutrophil-like cells which was associated with cutaneous pathology including epidermal hyperplasia, parakeratosis, and Munro’s microabscesses formation. Conclusion Collectively, these data support that IL-17A can play a key role in the pathogenesis of inflammation-associated arthritis and/or skin disease, as observed in PsA.

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“…Surprisingly, transgenic expression of hFcγRIIA-R 131 on a wild-type mouse background was associated with the spontaneous development of an RA-like joint pathology (140). Expression of hFcγRIIA indeed renders mice highly susceptible to various models of arthritis (140, 141), even if its expression is purposely restricted to neutrophils (142). Small inhibitors designed to bind antagonistically to hFcγRIIA were found to be protective (143), proposing a hFcγR-targeted therapy for RA.…”

Section: In Vivo Roles Of Human Fcγrs: Lessons From Mouse Models1mentioning

confidence: 99%

Contribution of Human FcÎ³Rs to Disease with Evidence from Human Polymorphisms and Transgenic Animal Studies

Gouel-Cheron²,

et al. 2014

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The biological activities of human IgG antibodies predominantly rely on a family of receptors for the Fc portion of IgG, FcγRs: FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, FcγRIIIB, FcRL5, FcRn, and TRIM21. All FcγRs bind IgG at the cell surface, except FcRn and TRIM21 that bind IgG once internalized. The affinity of FcγRs for IgG is determined by polymorphisms of human FcγRs and ranges from 2 × 104 to 8 × 107 M−1. The biological functions of FcγRs extend from cellular activation or inhibition, IgG-internalization/endocytosis/phagocytosis to IgG transport and recycling. This review focuses on human FcγRs and intends to present an overview of the current understanding of how these receptors may contribute to various pathologies. It will define FcγRs and their polymorphic variants, their affinity for human IgG subclasses, and review the associations found between FcγR polymorphisms and human pathologies. It will also describe the human FcγR-transgenic mice that have been used to study the role of these receptors in autoimmune, inflammatory, and allergic disease models.

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Transgenic mice expressing human FcγRIIa have enhanced sensitivity to induced autoimmune arthritis as well as elevated Th17 cells

Cited by 23 publications

References 49 publications

Shifting FcγRIIA-ITAM from activation to inhibitory configuration ameliorates arthritis

Shifting FcγRIIA-ITAM from activation to inhibitory configuration ameliorates arthritis

IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis

Contribution of Human FcÎ³Rs to Disease with Evidence from Human Polymorphisms and Transgenic Animal Studies

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