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Granulomas are a source of interleukin-33 expression in pulmonary and extrapulmonary sarcoidosis


Kempf, Werner; Zollinger, Therese; Sachs, Melanie; Ullmer, Elke; Cathomas, Gieri; Dirnhofer, Stephan; Mertz, Kirsten D (2014). Granulomas are a source of interleukin-33 expression in pulmonary and extrapulmonary sarcoidosis. Human Pathology, 45(11):2202-2210.

Abstract

Sarcoidosis is a chronic inflammatory disease characterized by noncaseating epithelioid granulomas. These granulomas consist of highly differentiated mononuclear phagocytes-epithelioid cells and multinucleated giant cells (MNGCs)-surrounded by a proinflammatory infiltrate. Interleukin-33 (IL-33) is an inflammatory cytokine that is constitutively expressed in barrier tissues such as skin and lung and up-regulated in inflammation. Because sarcoidosis occurs most frequently in lung and skin, we studied the expression of this cytokine by immunohistochemistry in these tissues from patients with sarcoidosis, with foreign body granulomas, with other granulomatous diseases, and in corresponding normal tissues. We identified nuclear IL-33 staining of epithelioid cells and MNGCs in biopsies of skin (18/25 patients, 72%) and lung (10/19 patients, 53%) sarcoidosis. In contrast, sarcoidal granulomas in lymph nodes did not show IL-33 expression. Other granulomatous diseases showed only occasional and weak IL-33 expression. In sarcoidosis, we found a strong correlation between IL-33 expression and systemic disease, presence of MNGCs, and an M2-like macrophage phenotype as assessed by CD163 staining. Therefore, we propose that IL-33 plays a critical role in pathogenesis and disease progression of sarcoidosis. Because IL-33 is less commonly and only weakly expressed in other granulomatous diseases, the detection of IL-33 might serve as an adjunctive diagnostic marker. IL-33 expression in sarcoidosis seems to be dependent on the specific tissue microenvironment of sarcoidal granulomas and represents a novel biomarker for systemic involvement.

Abstract

Sarcoidosis is a chronic inflammatory disease characterized by noncaseating epithelioid granulomas. These granulomas consist of highly differentiated mononuclear phagocytes-epithelioid cells and multinucleated giant cells (MNGCs)-surrounded by a proinflammatory infiltrate. Interleukin-33 (IL-33) is an inflammatory cytokine that is constitutively expressed in barrier tissues such as skin and lung and up-regulated in inflammation. Because sarcoidosis occurs most frequently in lung and skin, we studied the expression of this cytokine by immunohistochemistry in these tissues from patients with sarcoidosis, with foreign body granulomas, with other granulomatous diseases, and in corresponding normal tissues. We identified nuclear IL-33 staining of epithelioid cells and MNGCs in biopsies of skin (18/25 patients, 72%) and lung (10/19 patients, 53%) sarcoidosis. In contrast, sarcoidal granulomas in lymph nodes did not show IL-33 expression. Other granulomatous diseases showed only occasional and weak IL-33 expression. In sarcoidosis, we found a strong correlation between IL-33 expression and systemic disease, presence of MNGCs, and an M2-like macrophage phenotype as assessed by CD163 staining. Therefore, we propose that IL-33 plays a critical role in pathogenesis and disease progression of sarcoidosis. Because IL-33 is less commonly and only weakly expressed in other granulomatous diseases, the detection of IL-33 might serve as an adjunctive diagnostic marker. IL-33 expression in sarcoidosis seems to be dependent on the specific tissue microenvironment of sarcoidal granulomas and represents a novel biomarker for systemic involvement.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:November 2014
Deposited On:14 Jan 2015 12:48
Last Modified:08 Dec 2017 09:45
Publisher:Elsevier
ISSN:0046-8177
Publisher DOI:https://doi.org/10.1016/j.humpath.2014.07.011
PubMed ID:25200795

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