Oral tolerance inhibits atopic dermatitis-like type 2 inflammation in mice by modulating immune microenvironments.
BACKGROUND
Oral tolerance is immune unresponsiveness induced by oral administration of innocuous antigens. Oral administration of allergens has been shown to be effective for suppressing IgE production in allergic responses. However, whether oral tolerance has a role in protection from allergic skin inflammation has not been fully investigated. Here, we evaluated the potential protective role of oral tolerance in a murine model of atopic dermatitis (AD) and investigated the underlying immunologic mechanisms.


METHODS
Mice were fed with ovalbumin (OVA) in drinking water then epicutaneously sensitized by repeated application of OVA to tape-stripped skin. Skin biopsies were analyzed for immunohistopathologic features. Levels of antibodies in sera and intestinal washes were measured by ELISA. Flow cytometry and real-time PCR analysis of the skin and mesenteric lymph nodes (MLN) were performed to investigate the immunologic effects of oral tolerance in epicutaneous (EC) sensitization-induced allergic responses.


RESULTS
Induction of oral tolerance effectively inhibited inflammatory responses provoked by EC sensitization. Tolerogenic immune mediators were significantly increased in the skin and MLN of EC-sensitized mice following induction of oral tolerance. A marked increase in Il5 and Il13 expression and infiltration of eosinophils and type 2 innate lymphoid cells (ILC2) in the skin of EC-sensitized mice were significantly inhibited by oral tolerance.


CONCLUSIONS
Oral tolerance plays a protective role in the development of AD in a murine model by modulating immune microenvironments to be more favorable for immune regulation. This modulation involves inhibition of ILC2 infiltration in skin lesions.
Department of Dermatology, Gachon University Gil Medical Center, Incheon, Republic of Korea.
J O
JO
Baek
Department of Dermatology, Gachon University Gil Medical Center, Incheon, Republic of Korea.
J Y
JY
Roh
Department of Microbiology, School of Medicine, Gachon University, Incheon, Republic of Korea.
Y
Y
Jung
D000284:Administration, Oral; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D015415:Biomarkers; D060833:Cellular Microenvironment / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D003888:Desensitization, Immunologic / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin
atopic dermatitis; eosinophil; epicutaneous sensitization; oral tolerance; type 2 innate lymphoid cells