Digital immunohistological dissection of immune privilege collapse in syringotropic autoimmune diseases: Implication for the pathogenesis. Issue 1 (January 2021)

• Record Type: Journal Article
• Authors: Shimoda-Komatsu, Yurie; Yamazaki, Yoshimi; Tsukashima, Aki; Kimishima, Momoko; Ohyama, Manabu
• Is Part Of: Journal of dermatological science. Volume 101:Issue 1(2021)
• Page Start: 30
• Page End: 39
• Publication Date: 2021-01
• Subjects: AA alopecia areata -- α-MSH alpha-melanocyte stimulating hormone -- α-SMA alpha-smooth muscle actin -- ACR American College of Rheumatology -- BI brightness index -- EULAR European League Against Rheumatism -- HF hair follicle -- IDO indoleamine-2, 3-dioxygenase -- IFN-γ interferon-gamma -- IP immune privilege -- LE lupus erythematosus -- LPP lichen planopilaris -- MHC major histocompatibility complex -- MIF macrophage migration inhibitory factor -- mAb monoclonal antibody -- PBS phosphate buffered saline -- Scl-A scleroderma- atrophic type -- Scl-I sclerderma- inflammatory type -- SI staining index -- SjS Sjögren syndrome -- SwD sweat duct -- SwG sweat gland -- TGF-β transforming growth factor-beta -- TRLs Toll-like receptors; autoimmune diseases -- immune privilege -- digital image analysis -- sweat gland -- syringotropism; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2020.10.015
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: The existence of immune privilege (IP) in human sweat glands (SwGs) was first described by demonstrating differential expression of IP molecules The newly developed digital immunohistological microdissection technique allows quantitative evaluation of site-specific expression of target molecules in paraffin-embedded sections. Dysregulated expression of IP molecules may lead to IP collapse with induction of syringotropic cell infiltration in autoimmune/collagen disorders. The human skin organ culture combined with intratissue proinflammatory cytokine injection provides an ex vivo approach to investigating skin appendage IP. Abstract: Background: Syringotropic cell infiltration is a histological hallmark of some autoimmune diseases. However, its underlying mechanism remains unclear. Objectives: To assess the immune privilege (IP) of the human sweat gland (SwG) in homeostasis and in syringotropic autoimmune diseases. Methods: We combined quantitative digital image microdissection with immunohistochemisty to analyze IP molecule expression in SwG of normal and diseased skin. The human skin organ culture model was used to examine the influence of proinflammatory conditions on IP in SwG. Results: In the normal subjects ( n = 10), major histocompatibility complex (MHC) class І expression was significantly reduced in SwGs compared to the epidermis. In contrast, IP-guardians, macrophage migration inhibitory factor (MIF) and alpha-melanocyte stimulating hormone (α-MSH) were upregulated in SwGs. MHC class І was upregulated in whole SwGs in lupus erythematosus (LE; n = 7) and scleroderma/morphea (Scl; n = 9), whereas differential expression was noted only in the secretory portion in Sjögren's syndrome (SjS) ( n = 4). MIF expression level inversely correlated with that of MHC class I in all samples tested, and downregulation of α-MSH was detected in LE SwGs alone. The severity of inflammatory changes and MIF and ⍺-MSH expression were inversely correlated in LE. CD200 expression was decreased exclusively in atrophic stage of Scl. In a human skin organ culture model, intratissue injection of interferon-gamma up-regulated MHC class I and downregulated MIF and α-MSH. Conclusions: These findings indicate that SwGs enjoy IP. Dysregulated IP molecule expression may lead to SwG IP collapse and contribute to distinct inflammatory cell distribution in syringotropic autoimmune disorders.