Activated Leukocyte Cell Adhesion Molecule Modulates Th2 Immune Response in Atopic Dermatitis
10.4168/aair.2019.11.5.677
- Author:
Mi Seon OH
1
;
Jung Yeon HONG
;
Mi Na KIM
;
Eun Ji KWAK
;
Soo Yeon KIM
;
Eun Gyul KIM
;
Kyung Eun LEE
;
Yun Seon KIM
;
Hye Mi JEE
;
Seo Hyeong KIM
;
In Suk SOL
;
Chang Ook PARK
;
Kyung Won KIM
;
Myung Hyun SOHN
Author Information
1. Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. mhsohn@yuhs.ac
- Publication Type:Original Article
- Keywords:
ALCAM;
CD166;
atopic dermatitis;
type 2 helper T cells;
skin barrier
- MeSH:
Activated-Leukocyte Cell Adhesion Molecule;
Animals;
Dendritic Cells;
Dermatitis, Atopic;
Gene Expression;
Humans;
Immunoglobulins;
Immunological Synapses;
Lymph Nodes;
Mice;
Ovalbumin;
Skin;
T-Lymphocytes;
Water
- From:Allergy, Asthma & Immunology Research
2019;11(5):677-690
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Activated leukocyte cell adhesion molecule (ALCAM), a member of the immunoglobulin superfamily, is highly expressed on dendritic cells. ALCAM and its receptor CD6 are co-stimulatory molecules in the immunological synapse; their interaction is required for T cell activation. While atopic dermatitis (AD) is recognized as a T helper 2 (Th2)-mediated allergic disease, the role of ALCAM in its pathogenesis is unclear. METHODS: ALCAM levels were measured in the serum of AD patients and AD-induced murine model by ovalbumin treatment. We next investigated transepidermal water loss, clinical score, Th2-immune responses, skin barrier gene expression and T-cell activation using wild-type (WT) and ALCAM deficiency mice. An oxazolone-induced AD-like model was also established and analyzed using WT- and ALCAM-deficient mice. RESULTS: We found that serum ALCAM levels were elevated in pediatric AD patients as well as WT AD mice, whereas Th2-type cytokine production and AD symptoms were suppressed in ALCAM-deficient mice. In addition, CD4+ effector T-cell counts in murine skin and skin-draining lymph nodes were lower in ALCAM-deficient mice than in their WT counterparts. ALCAM deficiency was also linked to higher expression of skin barrier genes and number of lamellar bodies. CONCLUSIONS: These findings indicate that ALCAM may contribute to AD pathogenesis by meditating a Th2-dominant immune response and disrupting the barrier function of the skin.
