Digital immunohistological dissection of immune privilege collapse in syringotropic autoimmune diseases: Implication for the pathogenesis.
J Dermatol Sci
; 101(1): 30-39, 2021 Jan.
Article
em En
| MEDLINE
| ID: mdl-33183905
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 Ð 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 Ð 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 âº-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Doenças das Glândulas Sudoríparas
/
Glândulas Sudoríparas
/
Regulação da Expressão Gênica
/
Privilégio Imunológico
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Dermatol Sci
Assunto da revista:
DERMATOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão