Plasmacytoid dendritic cells orchestrate TLR7-mediated innate and adaptive immunity for the initiation of autoimmune inflammation.

Abstract

Endosomal toll-like receptor (TLR)-mediated detection of viral nucleic acids (NAs) and production of type I interferon (IFN-I) are key elements of antiviral defense, while inappropriate recognition of self NAs with the induction of IFN-I responses is linked to autoimmunity such as psoriasis and systemic lupus erythematosus. Plasmacytoid dendritic cells (pDCs) are cells specialized in robust IFN-I secretion by the engagement of endosomal TLRs, and predominantly express sialic acid-binding Ig-like lectin (Siglec)-H. However, how pDCs control endosomal TLR-mediated immune responses that cause autoimmunity remains unclear. Here we show a critical role of pDCs in TLR7-mediated autoimmunity using gene-modified mice with impaired expression of Siglec-H and selective ablation of pDCs. pDCs were shown to be indispensable for the induction of systemic inflammation and effector T-cell responses triggered by TLR7 ligand. pDCs aggravated psoriasiform dermatitis mediated through the hyperproliferation of keratinocytes and enhanced dermal infiltration of granulocytes and γδ T cells. Furthermore, pDCs promoted the production of anti-self NA antibodies and glomerulonephritis in lupus-like disease by activating inflammatory monocytes. On the other hand, Siglec-H regulated the TLR7-mediated activation of pDCs. Thus, our findings reveal that pDCs provide an essential link between TLR7-mediated innate and adaptive immunity for the initiation of IFN-I-associated autoimmune inflammation.

• Authors: Hideaki Takagi, Keiichi Arimura, Tomofumi Uto, Tomohiro Fukaya, Takeshi Nakamura, Narantsog Choijookhuu, Yoshitaka Hishikawa, Katsuaki Sato
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 24477 (Apr 14 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27075414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Toll-Like Receptor 7

Topics

• Adaptive Immunity
• Animals
• Autoimmune Diseases (physiopathology)
• Dendritic Cells (immunology)
• Dermatitis (physiopathology)
• Disease Models, Animal
• Glomerulonephritis (physiopathology)
• Immunity, Innate
• Inflammation (physiopathology)
• Mice
• Psoriasis (physiopathology)
• Skin (pathology)
• Toll-Like Receptor 7 (metabolism)