Interleukin-33 produced by M2 macrophages and other immune cells contributes to Th2 immune reaction of IgG4-related disease

• Published in: Scientific reports Vol. 7; no. 1; p. 42413
• Main Authors: Furukawa, Sachiko, Moriyama, Masafumi, Miyake, Kensuke, Nakashima, Hitoshi, Tanaka, Akihiko, Maehara, Takashi, Iizuka-Koga, Mana, Tsuboi, Hiroto, Hayashida, Jun-Nosuke, Ishiguro, Noriko, Yamauchi, Masaki, Sumida, Takayuki, Nakamura, Seiji
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.02.2017; Nature Publishing Group
• Subjects: 38/77; 631/250/2504/342; 631/250/38; 82/51; CD163 antigen; Cell activation; Cytokines; Dendritic cells; Epithelial cells; Gene expression; Germinal centers; Glands; Humanities and Social Sciences; Immune response; Immunofluorescence; Immunoglobulin G; Interleukin 13; Interleukin 4; Lymphocytes T; Macrophages; multidisciplinary; Science; Sjogren's syndrome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep42413

IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and marked infiltration of IgG4-positive cells in multiple organs. Interleukin-33 (IL-33) is a recently described cytokine that is secreted by damaged epithelial cells, macrophages, and dendritic cells, and potently activates helper T type 2 (Th2) immune responses, which have been suggested to play a major role in IgG4 production of IgG4-RD. Here, we assessed the expression of IL-33 and related molecules in the salivary glands (SGs) of patients with IgG4-RD versus that in patients with Sjögren’s syndrome (SS) and controls. Expression of IL-33 and its receptor (ST2) was strongly detected around ectopic germinal centers (GCs) in the SGs from patients with IgG4-RD, whereas IL-33 was expressed only in epithelial cells in patients with SS and controls. Moreover, IL-33 and CD68 + /CD163 + macrophages were mainly distributed around ectopic GCs in patients with IgG4-RD. Double immunofluorescence staining showed that IL-33 expression co-localized with CD68 + /CD163 + macrophages. Finally, mRNA expression levels of IL-33 showed a positive correlation to those of Th2 cytokines (IL-4 and IL-13) in patients with IgG4-RD. Our data suggest that IL-33 produced by M2 macrophages might contribute to the pathogenesis of IgG4-RD via aberrant activation of Th2 immune responses.