Abstract
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.
Highlights
Mikulicz’s disease (MD) and Küttner tumor (KT) affect the oral maxillofacial region, presenting with changes in facial appearance, such as persistent swollen of upper eyelids, parotid gland, and submandibular glands
IgG4-RD is well known as a systemic disorder that is characterized by elevated serum IgG4, marked infiltration of IgG4-positive plasma cells, and severe fibrosis with hyperplastic eGCs in affected lesions
They found that serum IL-33 and ST2 levels were increased in pSS patients and that IL-33 producing cells were mainly epithelial cells in salivary glands (SGs) from patients with pSS
Summary
Mikulicz’s disease (MD) and Küttner tumor (KT) affect the oral maxillofacial region, presenting with changes in facial appearance, such as persistent swollen of upper eyelids, parotid gland, and submandibular glands. To clarify the contribution of IL-33 to the pathogenesis of IgG4-RD, we examined infiltrating cells expressing IL-33 in SGs from patients with IgG4-RD. The mRNA expression levels of IL-33, ST2, and IL-4 in SGs from patients with SS and IgG4-RD were significantly higher than those in controls.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
