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Jacobs J Allergy Immunol. 2014 Dec;1(1). pii: 007.

Modulation of Immune response by Ultra-violet light in HLA class-II transgenic mice.

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Department of Immunology, Mayo Clinic, Rochester, MN, USA.
Department of Dermatology, Mayo Clinic, Rochester, MN, USA.
Department of Nephrology, Mayo Clinic, Rochester, MN, USA.
Department of Neurology, Mayo Clinic, Rochester, MN, USA.


Multiple Sclerosis (MS) is a chronic and debilitating disease of the central nervous system linked to both genetic and environmental factors. Among the genetic factors, MHC, especially HLA class-II, is strongly associated with predisposition to MS. Although in vitro studies have helped us understand some aspects of HLA class-II association with the disease, performing in vivo analysis is necessary in order to further understand this correlation. Studying the role of class-II genes in vivo is a difficult task due to the heterogeneity of human population, the complexity of MHC, and the strong linkage disequilibrium among different class-II genes. To overcome this challenge, we generated HLA class-II transgenic mice to study the role of these molecules in MS. Among the environmental factors linked with MS, ultra violet radiation (UVR)/vitamin-D is suggested to have protective effect against the development of the disease. Indeed, genetic studies have shown that presence of susceptible HLA-Class II and decrease in UVR exposure or vitamin D levels together increase risk of MS. Therefore, this study was designed to investigate the direct effect of UVR on immune response using novel humanized HLA-class II transgenic mice. HLA-class II transgenic mice expressing MS susceptible HLA-DR2 allele were treated with different doses of UVR (0.50-3.75 kJ/day) for seven consecutive days. T-cell proliferation, immune cell sub-populations and cytokines levels were analyzed. Our results show that treatment with UVR increased levels of regulatory CD4+FoxP3+ T cells and Gr1+ CD11b+ suppressive macrophages. Thus our study indicates that UVR modulates the immune response towards a tolerogenic phenotype in HLA-transgenic mice immunized with MOG35-55. Therefore, HLA class-II transgenic mice offer a novel tool to decipher the mechanism by which interaction between environmental and genetic factors play a role in predisposition and/or protection against development of MS.


EAE/MS; HLA-transgenic mice; MHC; cytokines; epitopes; neuroimmunology; regulatory cells; ultraviolet light; vitamin D


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