Alpha 1 antitrypsin inhibits dendritic cell activation and attenuates nephritis in a mouse model of lupus

Ahmed S. Elshikha, Yuanqing Lu, Mong Jen Chen, Mohammad Akbar, Leilani Zeumer, Andrea Ritter, Hanaa Elghamry, Mahmoud A. Mahdi, Laurence Morel, Sihong Song

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution and considerable mortality and morbidity. Although the pathogenesis of this disease remains elusive, over-reactive dendritic cells (DCs) play a critical role in the disease development. It has been shown that human alpha-1 antitrypsin (hAAT) has protective effects in type 1 diabetes and rheumatoid arthritis mouse models. In the present study, we tested the effect of AAT on DC differentiation and functions, as well as its protective effect in a lupusprone mouse model. We showed that hAAT treatment significantly inhibited LPS (TLR4 agonist) and CpG (TLR9 agonist) -induced bone-marrow (BM)-derived conventional and plasmacytoid DC (cDC and pDC) activation and reduced the production of inflammatory cytokines including IFN-I, TNF-α and IL-1β. In MRL/lpr mice, hAAT treatment significantly reduced BM-derived DC differentiation, serum autoantibody levels, and importantly attenuated renal pathology. Our results for the first time demonstrate that hAAT inhibits DC activation and function, and it also attenuates autoimmunity and renal damage in the MRL/lpr lupus model. These results imply that hAAT has a therapeutic potential for the treatment of SLE in humans.

Original languageEnglish (US)
Article numbere0156583
JournalPloS one
Volume11
Issue number5
DOIs
StatePublished - May 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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