Journal
NATURE MEDICINE
Volume 16, Issue 6, Pages 713-U119Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2150
Keywords
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Funding
- Interdisciplinary Center of Clinical Research [Lo2/017/07, Vo2/014/09]
- German Cancer Society [107891]
- Federal Ministry of Education and Research [AID-Net]
- German Research Association [Lo817/21]
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Mechanisms linking innate immunity and autoimmune responses are poorly understood(1). Myeloid-related protein-8 (Mrp8) and Mrp14 are damage-associated molecular pattern molecules (DAMPs) highly upregulated in various autoimmune disorders. We show in a mouse autoimmune model that local Mrp8 and Mrp14 production is essential for the induction of autoreactive CD8(+) T cells and the development of systemic autoimmunity. This effect is mediated via Toll-like receptor 4 (TLR4) signaling leading to increased interleukin-17 (IL-17) expression. Notably, expression of Mrp8 and Mrp14 was upregulated in cutaneous lupus erythematosus, and stimulation of CD8(+) T cells from individuals with lupus erythematosus with MRP proteins resulted in an upregulation of IL-17, suggesting a key role for MRP8 and MRP14 for the development of autoreactive lymphocytes during human autoimmunity as well. These results demonstrate a link between local expression of DAMP molecules and the development of systemic autoimmunity.
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