Category: Autoimmune neurologic diseases
Multiple sclerosis (MS) is an autoimmune disease characterized by T cell-mediated destruction of myelinated axon sheaths in the central nervous system. Topical application of the vitamin D analogue, calcipotriol, can abrogate skin hypersensitivity responses in a T cell-dependent manner. We aim to test whether topical calcipotriol or tretinoin (vitamin A), a similarly immunomodulatory compound, can modulate the disease course of experimental autoimmune encephalitis (EAE), a mouse model of MS. We hypothesize that topical treatment with calcipotriol or tretinoin reduces EAE disease severity by reducing the generation of encephalitogenic T cells and increasing the number of regulatory T cells. Mice were pre-treated with tretinoin, calcipotriol, or vehicle for 2 days once daily before induction of EAE. Mice were monitored for up to 28 days, scored and weighed daily. Lymph nodes and spleens were harvested for flow cytometric analysis of T cell subsets and cytokine expression, and spinal cord sections were collected for histological study. Topical pre-treatment with tretinoin, but not calcipotriol, reduced the severity of EAE as reflected by lower clinical disease scores and sustained maintenance of body weight. Immune cell phenotype analysis showed reduced expression of interferon-gamma in CD4 and CD8 T cell compartments from lymphoid organs of animals pre-treated with tretinoin. The nature of topical immunomodulation as a non-invasive therapeutic intervention makes it an appealing treatment option. Further studies are warranted to verify the efficacy and mechanisms of topical retinoids on modulation of systemic immunity.
Paulina Piesik– MD-PhD Candidate, BC Children's Hospital Research
Laura Sly– Assistant Professor, Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine, University of British Columbia, BC Children's Hospital Research
Jan Dutz– Professor, Department of Dermatology and Skin Science, Faculty of Medicine, University of British Columbia, BC Children's Hospital Research