Session Title: Systemic Lupus Erythematosus - Animal Models
Session Type: Abstract Submissions (ACR)
Background/Purpose: Self antigens are taken from tissues to local lymphoid organs to acquire ability to avoid self-reactivity. This important immune function is accomplished by dendritic cell (DC) populations that primarily reside in tissues. We posit that a defect in the migration of tissue-resident DCs may predispose to autoimmunity in a tissue-specific manner; and an improved migration of tissue-specific DC may ameliorate disease in the respective organ. We have previously reported that lupus dermatitis-prone MRL mice exhibit a profound defect in the migration of skin-resident DC. Here, we investigated the effect of improved skin-DC migration on lupus dermatitis and determined mechanisms that regulate the migration of tissue-resident DC from tissues to lymph nodes
Methods: Skin and cutaneous lymph nodes from MRL-lpr mice and MHC-matched control mice and γδ T cell-deficient mice were analyzed for Langerhans DC and skin-resident invariant γδ T cells before and after treatment with a glycolipid αGalCer that was previously shown to ameliorate lupus dermatitis, without affecting disease in other organs.
Results: MRL mice that exhibit reduced skin-DC migration had reduced skin-resident γδ T cells, whereas treatment with αGalCer reduced the severity of lupus dermatitis and restored skin-γδ T cells and skin-DC migration. This effect of αGalCer was independent of its effect on invariant natural killer T cells, but required the presence of lipid antigen presenting molecule CD1d. We further show that gd T cell-deficient mice had reduced skin-DC migration in vivo, and skin-gd T cells directly promoted the migration of skin-DC in vitro via CD40L–CD40 interaction.
Conclusion: Our data elucidate a new mechanism of regulation of skin-DC homeostasis whereby skin-gd T cells normally facilitate skin-DC migration from skin to cutaneous lymph node. Such ‘local’ control of migratory behavior of tissue-DC can regulate immune response in a tissue-specific manner. This mechanism of skin-DC homeostasis is disrupted in lupus dermatitis, but can be repaired by treatment with a glycolipid.
R. R. Singh,
M. A. Gutierrez,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/treatment-with-a-glycolipid-ameliorates-lupus-dermatitis-and-expands-skin-aa-t-cells-that-promote-the-migration-of-langerhans-dendritic-cells/