The Toll-like receptor 4 ligands Mrp8 and Mrp14 are crucial in the development of autoreactive CD8+ T cells.

Karin Loser, Thomas Vogl, Maik Voskort, Aloys Lueken, Verena Kupas, Wolfgang Nacken, Lars Klenner, Annegret Kuhn, Dirk Foell, Lydia Sorokin, Thomas A Luger, Johannes Roth, Stefan Beissert

Department of Dermatology, University of Münster, Münster, Germany. loserk@uni-muenster.de

Nature medicine 2010 Jun

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Mechanisms linking innate immunity and autoimmune responses are poorly understood. 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.

Citation

Karin Loser, Thomas Vogl, Maik Voskort, Aloys Lueken, Verena Kupas, Wolfgang Nacken, Lars Klenner, Annegret Kuhn, Dirk Foell, Lydia Sorokin, Thomas A Luger, Johannes Roth, Stefan Beissert. The Toll-like receptor 4 ligands Mrp8 and Mrp14 are crucial in the development of autoreactive CD8+ T cells. Nature medicine. 2010 Jun;16(6):713-7