Preferential M2 macrophages contribute to fibrosis in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease

Sachiko Furukawa, Masafumi Moriyama, Akihiko Tanaka, Takashi Maehara, Hiroto Tsuboi, Mana Iizuka, Jun Nosuke Hayashida, Miho Ohta, Takako Saeki, Kenji Notohara, Takayuki Sumida, Seiji Nakamura

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) is characterized by bilateral swelling of glandular tissues with extensive fibrosis, and is immunologically considered a Th2-predominant disease. Recent studies reported that alternatively activated (M2) macrophages enhanced Th2 immune responses and fibrosis by production of pro-fibrotic factors (IL-10, IL-13 and CCL18). Therefore, we examined the association between M2 macrophages and fibrosis in submandibular glands from 7 patients with IgG4-DS, 10 patients with chronic sialoadenitis, 10 patients with Sjögren's syndrome, and 10 healthy subjects. The number of M2 macrophages in SMGs from patients with IgG4-DS was also significantly higher than in the other groups. Double immunofluorescence staining showed that IL-10 and CCL18 expression co-localized with M2 macrophage-marker (CD163). Furthermore, the SMG fibrosis score was positively correlated with the frequency of M2 macrophages in only IgG4-DS. These results indicate that IL-10 and CCL18 secreted by preferential M2 macrophages possibly play a key role in the development of severe fibrosis in IgG4-DS.

Original languageEnglish
Pages (from-to)9-18
Number of pages10
JournalClinical Immunology
Volume156
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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