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Clin Immunol. 2015 Jan;156(1):9-18. doi: 10.1016/j.clim.2014.10.008. Epub 2014 Oct 29.

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

Author information

1
Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
2
Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan. Electronic address: moriyama@dent.kyushu-u.ac.jp.
3
Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
4
Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Japan.
5
Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan.

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.

KEYWORDS:

CCL18; Fibrosis;; IL-10;; IgG4-related dacryoadenitis and sialoadenitis;; M2 macrophage;

PMID:
25450336
DOI:
10.1016/j.clim.2014.10.008
[Indexed for MEDLINE]
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