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Aberrant interleukin‐1 signalling does not increase susceptibility of mice to NOD 2‐dependent uveitis
Author(s) -
Lee Ellen J,
Allensworth Jordan J,
Clowers Jenna S,
Rosenzweig Holly L
Publication year - 2014
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/ceo.12438
Subject(s) - medicine , nod , uveitis , immunology , signalling , interleukin , cytokine , microbiology and biotechnology , endocrinology , diabetes mellitus , biology
Background NOD2 is the genetic cause of B lau syndrome, an autoinflammatory disease that manifests as coincident uveitis and arthritis. Since dysregulation of IL ‐1 signalling is considered a pathogenic mechanism in a number of related autoinflammatory conditions, we examined the extent to which unimpeded interleukin ( IL )‐1 signalling influences NOD 2‐dependent inflammation of the eye versus the joint. Methods Mice deficient for IL ‐1 R antagonist ( IL ‐1 R a) were administered the NOD 2 agonist muramyl dipeptide ( MDP ) by systemic (intraperitoneal) or local (intraocular and/or intra‐articular) injections. NOD 2‐deficient mice received an intraocular injection of recombinant IL ‐1β. Uveitis was evaluated by intravital videomicroscopy and histopathology, and arthritis was assessed by near‐infrared imaging and histopathology. Ocular levels of IL ‐1α, IL ‐1β and IL ‐1 R a were quantified by enzyme‐linked immunosorbent assay. Results IL ‐1 R a deficiency did not render mice more responsive to systemic exposure of MDP . Despite the increased production of IL ‐1 R agonists IL ‐1α and IL ‐1β in response to intraocular injection of MDP , deficiency in IL ‐1 R a did not predispose mice to MDP ‐triggered uveitis, albeit intravascular cell rolling and adherence were exacerbated. NOD 2 expression was dispensable for the potential of IL ‐1 to elicit uveitis. However, we find that IL ‐1 R a does play an important protective role in arthritis induced locally by MDP injection in the joint. Conclusions Our findings highlight the complexity of NOD 2 activation and IL ‐1 signalling effects that can be compounded by local environmental factors of the target organ. These observations may impact how we understand the molecular mechanisms by which NOD 2 influences inflammation of the eye versus joint, and consequently, treatment options for uveitis versus arthritis.