Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis

By A. M. Lin, Cory J. Rubin, R. Khandpur, J. Y. Wang, Marybeth Riblett, S. Yalavarthi, Eneida C. Villanueva, P. Shah, M. Kaplan, Allen T. Bruce. Journal of Immunology, 2011

912 citations recorded by the source corpus.

IL-17 and IL-23 are known to be absolutely central to psoriasis pathogenesis because drugs targeting either cytokine are highly effective treatments for this disease. The efficacy of these drugs has been attributed to blocking the function of IL-17–producing T cells and their IL-23–induced expansion. However, we demonstrate that mast cells and neutrophils, not T cells, are the predominant cell types that contain IL-17 in human skin. IL-17+ mast cells and neutrophils are found at higher densities than IL-17+ T cells in psoriasis lesions and frequently release IL-17 in the process of forming specialized structures called extracellular traps. Furthermore, we find that IL-23 and IL-1β can induce mast cell extracellular trap formation and degranulation of human mast cells. Release of IL-17 from innate immune cells may be central to the pathogenesis of psoriasis, representing a fundamental mechanism by which the IL-23–IL-17 axis mediates host defense and autoimmunity.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/fd69b82533137de3ba89b0bd25d5939546bdd6a0

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In Immunology

1. J. Krueger
2. M. Lowes
3. M. Suárez‐Fariñas
4. C. Rosales
5. M. Radic
6. M. Kaplan

Citations in the corpus

• Neutrophil Extracellular Traps and Its Implications in Inflammation: An Overview (2017, background): “have shown that IL-17 is abundantly produced by neutrophils and mast cells, both of which are found in the cellular infiltrates of psoriatic plaques (123).”
• NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis (2013, methodology): “Of potential relevance to RA pathogenesis, NETs have the capacity to externalize proinflammatory, immunostimulatory molecules and various autoantigens (13, 14, 17).”
• Immunology of Psoriasis (2014, methodology): “NETs have been identified in psoriasis by staining for nucleic acid with DAPI and neutrophil elastase (96, 97).”
• Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types? (2018, background): “These LDNs have been found in many other pathological conditions including sepsis (Morisaki et al., 1992), psoriasis (Lin et al., 2011), HIV infection (Cloke et al., 2012), asthma (Fu et al., 2014), ANCA-associated vasculitis (Grayson et al., 2015), and malaria (Rocha et al., 2015).”
• Netting neutrophils induce endothelial damage, infiltrate tissues and expose immunostimulatory molecules in systemic lupus erythematosus (2011, background): “Furthermore, neutrophils can externalize IL-17 through NETosis in skin and peripheral blood from patients with psoriasis (29).”
• Neutrophil extracellular traps (NETs): Double-edged swords of innate immunity (2012, background): “diseases such as SLE and psoriasis (11, 24, 26, 65).”