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Imiquimod-induced dermatitis impairs thymic tolerance of autoreactive CD4+ T cells to desmoglein 3
- Source :
- Journal of Dermatological Science. 100:166-174
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Background The thymus plays an essential role in removing autoreactive T cells. Autoantigen-expressing thymic epithelial cells (TECs) contribute to the tolerogenic process. The thymus transiently shrinks as an acute thymic involution (ATI) under various inflammatory conditions. However, whether ATI occurs during local skin inflammation remains unclear, as does its influence on thymic immune tolerance. Objective We investigated whether imiquimod-induced dermatitis causes ATI and impairs thymic immune tolerance against desmoglein 3 (Dsg3), an epidermal autoantigen of pemphigus vulgaris. Methods 5% imiquimod cream was applied daily, at 62.5 mg/day (high dose group) or 31.25 mg/day (low dose group), for 1 week on the back of wild-type mice, and to wild-type mice that had undergone bone-marrow transplantation from Dsg3-specific T-cell receptor (TCR) transgenic-Rag2−/− mice. Next, thymocytes, TECs and other immune cells were analyzed by flow cytometry. TEC-associated Dsg3 expression was also analyzed by immunofluorescence staining. Results Thymus weight and thymocyte number in all developmental stages decreased in a dose-dependent manner under imiquimod-induced dermatitis. The number of total TECs, specifically medullary, but not cortical, TECs, decreased in high and low dose groups. Accordingly, the number of Dsg3-experssing UEA-1+keratin 5+mTEC decreased in the thymus during imiquimod-induced dermatitis. Although Dsg3-sepcific transgenic thymocytes was usually deleted in the thymus under physiological condition by central tolerance, Dsg3-sepcific transgenic CD4+CD8− thymocytes significantly increased in number under imiquimod-induced dermatitis. Conclusion These findings indicate a crosstalk between skin and thymus in adult mice and suggest that skin inflammation may impair thymic tolerance to autoantigens, such as Dsg3.
- Subjects :
- 0301 basic medicine
education.field_of_study
Pemphigus vulgaris
Dermatology
Biology
medicine.disease
Biochemistry
Immune tolerance
Acute Thymic Involution
Transplantation
030207 dermatology & venereal diseases
03 medical and health sciences
Thymocyte
030104 developmental biology
0302 clinical medicine
Immune system
Desmoglein 3
Immunology
medicine
Central tolerance
education
Molecular Biology
Subjects
Details
- ISSN :
- 09231811
- Volume :
- 100
- Database :
- OpenAIRE
- Journal :
- Journal of Dermatological Science
- Accession number :
- edsair.doi...........e3f086be7d0f6f92548bcd91f43fbfb3