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

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.

• Authors: 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
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 156 Issue 1 Pg. 9-18 (Jan 2015) ISSN: 1521-7035 [Electronic] United States
• PMID: 25450336 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014. Published by Elsevier Inc.

Chemical References

• CCL18 protein, human
• Chemokines, CC
• Immunoglobulin G
• Interleukin-10

Topics

• Adult
• Aged
• Chemokines, CC (genetics, metabolism)
• Dacryocystitis (physiopathology)
• Female
• Gene Expression Profiling
• Gene Expression Regulation
• Humans
• Immunoglobulin G (metabolism)
• Immunohistochemistry
• Interleukin-10 (genetics, metabolism)
• Macrophages (metabolism)
• Male
• Middle Aged
• Mikulicz' Disease (physiopathology)
• Polymerase Chain Reaction
• Severity of Illness Index
• Sialadenitis (physiopathology)
• Sjogren's Syndrome (physiopathology)
• Submandibular Gland (physiopathology)