Interleukin 13-positive mast cells are increased in immunoglobulin G4-related sialadenitis

Abstract

Interleukin (IL)-13 is a T helper 2 (Th2) cytokine that plays important roles in the pathogenesis of asthma. IL-13 induces hypersensitivity of the airways, increased mucous production, elevated serum immunoglobulin (Ig) E levels, and increased numbers of eosinophils. Many patients with IgG4-related disease have allergic backgrounds and show elevated serum IgE levels and an increase in the number of eosinophils. Upregulation of Th2/regulatory T (Treg) cytokines, including IL-13, has been detected in affected tissues of patients with IgG4-related disease. We previously reported that mast cells might be responsible for the production of the Th2/Treg cytokines IL-4, IL-10, and transforming growth factor (TGF)-β1 in IgG4-related disease. In this study, immunohistochemical analysis showed increased numbers of IL-13-positive mast cells in IgG4-related disease, which suggests that mast cells also produce IL-13 and contribute to elevation of serum IgE levels and eosinophil infiltration in IgG4-related disease.

Factors related to renal cortical atrophy development after glucocorticoid therapy in IgG4-related kidney disease: a retrospective multicenter study

“…In contrast to pre-treatment renal function, the impact of serum IgE elevation on renal prognosis has not thus far been documented in IgG4-RKD. Concerning the pathophysiology of IgG4-RD, however, upregulation of T helper (Th) 2 cytokines including interleukin (IL)-4 and IL-13, which promote IgE production, in the affected lesions have been reported [26–29]. Furthermore, it has been indicated that such Th2 cytokines, especially IL-13, play a dominant role in the fibrosis observed in Th2-upregulated conditions [30, 31].…”

Upregulated interleukins (IL-6, IL-10, and IL-13) in immunoglobulin G4-related aortic aneurysm patients

“…For cytokine detection, previous studies used quantitative real-time PCR with RNA extracted from frozen tissue of affected organs or fluorescent dual immunohistochemical analysis of frozen tissue samples. [6][7][8][9] However, when endovascular aortic replacement for AAA became popular, obtaining new frozen samples of IgG4-AAs for estimates became difficult. Our study depended on data from formalin-fixed, paraffin-embedded slides stored for 1 to 8 years.…”

“…1 Two recent reports have shed new light on increased mast cell infiltration in IgG4-related sialadenitis. 7,8 In response to IgE stimulation, mast cells secrete various mediators, including IL-6. 37 A recent report on cutaneous IgG4-RD found that IC IL-6 mark the 75th and 25th percentiles, respectively, and the whiskers above and below the box extend 1.5 interquartile range in either direction.…”

“…Peripheral blood mononuclear cells collected from IgG4-RD patients produced more T-helper 2 (Th2)-type cytokines (eg, interleukin [IL]-4, IL-5, IL-10, and IL-13) than Th1 cytokines, such as interferon (IFN)-g. 3 Tissue examination revealed Th2-type cytokine overproduction in several organs affected by IgG4-RD. [4][5][6][7][8] Regulatory T cells (Tregs) may be important in autoimmune disorder development. Two regulatory cytokines, IL-10 and transforming growth factor (TGF)-b, are also overexpressed in IgG4-related pancreatitis and tubulointerstitial nephritis.…”

IgG4-Related Disease

“…Co-localization analyses on cells expressing both GATA3 and IL-4, IL-5, or IL-13 have not been performed in the lesions of IgG4-RD patients. Therefore, it is possible that IL-4 and IL-13 may be derived from other types of cells, such as T follicular helper (Tfh) cells (Akiyama et al 2015;Maehara et al 2012;Moriyama et al 2014) and mast cells (Takeuchi et al 2014(Takeuchi et al , 2015 rather than conventional TH2 cells.…”