Journal
JOURNAL OF IMMUNOLOGY
Volume 200, Issue 9, Pages 3100-3108Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1701206
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Funding
- Diabetes Research Center grant (National Institutes of Health) [P30 DK063720]
- Marie Curie International Outgoing Fellow: FP7-PEOPLE-IOF [327244]
- National Institutes of Health [K08-AR062064, DP2-AR068130, R21-AR066821]
- Burroughs Wellcome Fund [CAMS-1010934]
- Scleroderma Research Foundation grant
- National Psoriasis Foundation translational grant
- Dermatology Foundation Stiefel Scholar Award in Autoimmune and Connective Tissue Diseases
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Migratory dendritic cell (DC) subsets deliver tissue Ags to draining lymph nodes (DLNs) to either initiate or inhibit T cell-mediated immune responses. The signals mediating DC migration in response to tissue self-antigen are largely unknown. Using a mouse model of inducible skin-specific self-antigen expression, we demonstrate that CD103(+) dermal DCs (DDCs) rapidly migrate from skin to skin DLN (SDLNs) within the first 48 h after Ag expression. This window of time was characterized by the preferential activation of tissue-resident Ag-specific effector T cells (Teffs), with no concurrent activation of Ag-specific Teffs in SDLNs. Using genetic deletion and adoptive transfer approaches, we show that activation of skin-resident Teffs is required to drive CD103(+) DDC migration in response to tissue self-antigen and this Batf3-dependent DC population is necessary to mount a fulminant autoimmune response in skin. Conversely, activation of Ag-specific Teffs in SDLNs played no role in DDC migration. Our studies reveal a crucial role for skin-resident T cell-derived signals, originating at the site of self-antigen expression, to drive DDC migration during the elicitation phase of an autoimmune response.
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