An Integrated Classification of Pediatric Inflammatory Diseases, Based on the Concepts of Autoinflammation and the Immunological Disease Continuum

McGonagle, Dennis; Aziz, Azad; Dickie, Laura; McDermott, Michael F.

doi:10.1203/pdr.0b013e31819dbd0a

Cited by 74 publications

(44 citation statements)

References 83 publications

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“…Furthermore, this is the first report of IL-23-amplified induction/production of IL-1␤ and demonstrates that IL-23 has the potential to potently amplify IL-1␤-mediated processes, such as neutrophil inflammation and autoinflammation (21,27,39). This synergistic induction can create autoamplification loops that promote dysfunctional inflammation, as has been documented with IL-1␤ (13,58,59).…”

Section: Discussionsupporting

confidence: 60%

Interleukin-23-Mediated Inflammation in Pseudomonas aeruginosa Pulmonary Infection

et al. 2012

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Pseudomonas aeruginosa is an opportunistic pathogen that is capable of causing acute and chronic pulmonary infection in the immunocompromised host. In the case of cystic fibrosis (CF), chronic P. aeruginosa infection causes increased mortality by promoting overly exuberant airway inflammation and cumulative lung damage. Identifying the key regulators of this inflammation may lead to the development of new therapies that improve P. aeruginosa-related mortality. We report here that interleukin-23 (IL-23), the cytokine most clearly tied to IL-17-mediated inflammation, also promotes IL-17-independent inflammation during P. aeruginosa pulmonary infection. During the early innate immune response, prior to IL-17 induction, IL-23 acts synergistically with IL-1␤ to promote early neutrophil (polymorphonuclear leukocyte [PMN]) recruitment. However, at later time points, IL-23 also promoted IL-17 production by lung ␥␦ T cells, which was greatly augmented in the presence of IL-1␤. These studies show that IL-23 controls two independent phases of neutrophil recruitment in response to P. aeruginosa infection: early PMN emigration that is IL-17 independent and later PMN emigration regulated by IL-17. Pseudomonas aeruginosa pulmonary infection occurs in immunocompromised hosts and is associated with significant morbidity and mortality. The pathogen induces a robust neutrophil response that causes significant airway damage and does not always eliminate the pathogen. In cystic fibrosis (CF), where infection is chronic, the inflammation causes cumulative airway damage that is a major contributor to morbidity and mortality (41,46,62). Identifying the immune mediators that promote this inflammation is the first step in developing new therapies that can improve outcomes in chronic P. aeruginosa pulmonary infection.We and others have previously shown that airway interleukin-23 (IL-23) and IL-17 levels correlate with infection status and inflammation in individuals with CF (12,15,38) and that lymphocytes from CF-derived draining lymph nodes produce higher levels of IL-17 than non-CF disease controls (3). We have also shown that both IL-23 and IL-17 are critical for neutrophil recruitment in a murine model of chronic P. aeruginosa pulmonary infection (14). While these data demonstrate that the IL-23/ IL-17 proinflammatory axis is active during P. aeruginosa airway infection and in CF, the studies did not isolate the actions of IL-23 from those of IL-17.Historically, IL-17 has been credited with promoting both neutrophil recruitment and granulopoiesis through its induction of neutrophil growth factors and chemokines, including IL-6, granulocyte colony-stimulating factor (G-CSF), keratinocyte chemoattractant (KC), and macrophage inflammatory protein 2 (MIP-2) (14,24,30,38,49,54,64). IL-23, a recently identified IL-12 family member (42, 60), has been primarily characterized in the context of this Th17 response (1,25,33). Of note, however, IL-23-overexpressing mice have a hyperinflammatory phenotype and notable elevations in serum IL-1␤ and t...

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Section: Discussionsupporting

confidence: 60%

Interleukin-23-Mediated Inflammation in Pseudomonas aeruginosa Pulmonary Infection

et al. 2012

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“…The present findings and possible relevance of the tendon disease localization, particularly in oligoarticular JIA, take on increasing importance with the realization that autoimmunity as embodied by aberrant B and T cell responses is less likely to be the primary driver in many categories of JIA 9 and in inflammation against self in general 10 . Given the relative rarity of JIA, academic pediatric rheumatologists need to collaborate to create inception cohorts and link baseline synovial and tendon-based disease to other features including antinuclear antibody status and uveitis.…”

Section: Rheumatologymentioning

confidence: 72%

Towards a New Clinico-Immunopathological Classification of Juvenile Inflammatory Arthritis: Figure 1.

McGonagle¹,

Benjamin²

2009

J Rheumatol

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“…Besides classical PIDs, new disorders are being increasingly diagnosed, which are associated with complex defects of immune functions [3]. Nowadays, it is a well accepted concept that the clinical spectrum of PID includes inflammatory, autoimmune and lymphoproliferation symptoms as well as recurrent or severe infections.…”

Section: Introductionmentioning

confidence: 99%

Clinical immunology Primary Immunodeficiency Diseases in two neighboring pediatric centers: registry data bring out a wide spectrum of diseases with complex clinical presentations

Pirrone¹,

Markelj²,

Piscianz³

et al. 2012

cejoi

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An Integrated Classification of Pediatric Inflammatory Diseases, Based on the Concepts of Autoinflammation and the Immunological Disease Continuum

Cited by 74 publications

References 83 publications

Interleukin-23-Mediated Inflammation in Pseudomonas aeruginosa Pulmonary Infection

Interleukin-23-Mediated Inflammation in Pseudomonas aeruginosa Pulmonary Infection

Towards a New Clinico-Immunopathological Classification of Juvenile Inflammatory Arthritis: Figure 1.

Clinical immunology Primary Immunodeficiency Diseases in two neighboring pediatric centers: registry data bring out a wide spectrum of diseases with complex clinical presentations

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