Upregulation and pathogenic roles of CCL18-CCR8 axis in IgG4-related disease
Creators: name: Tsuboi, Hiroto
name: Iizuka-Koga, Mana
name: Asashima, Hiromitsu
name: Takahashi, Hiroyuki
name: Kudo, Hanae
name: Ono, Yuko
name: Fumika Honda
name: Iizuka, Akira
name: Segawa, Seiji
name: Abe, Saori
name: Yagishita, Mizuki
name: Yokosawa, Masahiro
name: Kondo, Yuya
name: Moriyama, Masafumi
name: Matsumoto, Isao
name: Nakamura, Seiji
name: Sumida, Takayuki
Publisher: name: Taylor & Francis
Year: 2019
Subjects: subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Molecular Biology
subject: Physiology
subject: Immunology
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: Developmental Biology
subject: Cancer
subject: Hematology

description: <b>Objectives:</b> To determine the protein expression level, expressing cell types, and pathogenic roles of chemokine (C-C motif) ligand 18 (CCL18) and its receptor chemokine (C-C motif) receptor 8 (CCR8) in affected tissues of patients with IgG4-related disease (IgG4-RD). <b>Methods:</b> The protein expression levels of CCL18 in labial salivary glands (LSGs) assessed by immunofluorescence (IF) staining were compared among patients with IgG4-RD (<i>n</i> = 3), primary Sjögren’s syndrome (pSS; <i>n</i> = 4), and control subjects (<i>n</i> = 5). CCL18 expression levels in macrophages, CD11c<sup>+</sup> cells, B cells, and plasmacytes in LSGs were examined by double IF staining. The protein expression levels of CCR8 and expressing cells (T, B cells, and plasmacytes) in LSGs were also compared among patients with IgG4-RD, pSS, and control subjects by double IF staining. The effects of the CCL18-CCR8 axis on total IgG, IgG2, and IgG4 production by peripheral blood mononuclear cells (PBMCs) stimulated with CD40L, IL-4, IL-10, and IL-21 were examined by <i>in vitro</i> assays. <b>Results:</b> CCL18 was specifically upregulated in LSGs of patients with IgG4-RD, compared with only a few cells in pSS patients and none of the controls. The numbers of CCL18-producing macrophages, CD11c<sup>+</sup> cells, and plasmacytes in LSGs were significantly higher in IgG4-RD patients than in pSS patients and control (<i>p</i> <b>Conclusion:</b> CCL18-CCR8 axis was upregulated in LSGs of patients with IgG4-RD, suggesting possible roles of this axis in the pathogenesis of IgG4-RD.Key messagesThe CCL18-CCR8 axis in labial salivary glands (LSGs) and lacrimal glands of IgG4-RD patients was specifically upregulated compared with primary Sjögren’s syndrome and control subjects.This axis might be a potentially novel therapeutic target in IgG4-RD, based on its important etiopathogenic roles, such as chemotaxis of various cells, induction of fibrosis, and enhancement of IgG4 production. The CCL18-CCR8 axis in labial salivary glands (LSGs) and lacrimal glands of IgG4-RD patients was specifically upregulated compared with primary Sjögren’s syndrome and control subjects. This axis might be a potentially novel therapeutic target in IgG4-RD, based on its important etiopathogenic roles, such as chemotaxis of various cells, induction of fibrosis, and enhancement of IgG4 production.