PMID- 31943822 OWN - NLM STAT- MEDLINE DCOM- 20200722 LR - 20220716 IS - 2326-5205 (Electronic) IS - 2326-5191 (Linking) VI - 72 IP - 6 DP - 2020 Jun TI - DNA Vaccination With Hsp70 Protects Against Systemic Lupus Erythematosus in (NZB x NZW)F1 Mice. PG - 997-1002 LID - 10.1002/art.41202 [doi] AB - OBJECTIVE: To address whether a targeted modulation of the abnormal expression of Hsp70 and autoantibodies against this molecule in systemic lupus erythematosus can influence disease. METHODS: Lupus-prone (NZB x NZW)F1 mice that had been DNA-vaccinated with plasmids encoding Hsp70 and controls were monitored for lupus disease parameters including anti-double stranded DNA (anti-dsDNA) autoantibodies and cytokines using enzyme-linked immunosorbent assay, and for kidney function and pathology. The phenotypic and numerical changes in relevant immune cells were evaluated by flow cytometry, and cell function was assessed. RESULTS: Mice that had been DNA-vaccinated with Hsp70 displayed marked suppression of anti-dsDNA antibody production, reduced renal disease, and antiinflammatory responses that are associated with a significantly extended survival, compared to controls. These protective effects in Hsp70-vaccinated mice were associated with an induction of tolerogenic immune responses and an expansion of functional Treg cells. CONCLUSION: DNA vaccination with Hsp70 suppresses murine lupus by inducing tolerogenic immune responses and antiinflammatory immune responses associated with reduced disease manifestations and increased mouse survival. CI - (c) 2020, American College of Rheumatology. FAU - Liu, Aijing AU - Liu A AD - University of California, Los Angeles. FAU - Ferretti, Concetta AU - Ferretti C AD - University of California, Los Angeles. FAU - Shi, Fu-Dong AU - Shi FD AD - Barrow Neurological Institute, Phoenix, Arizona. FAU - Cohen, Irun R AU - Cohen IR AD - The Weizmann Institute of Science, Rehovot, Israel. FAU - Quintana, Francisco J AU - Quintana FJ AD - Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - La Cava, Antonio AU - La Cava A AUID- ORCID: 0000-0002-8839-0933 AD - University of California, Los Angeles. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200430 PL - United States TA - Arthritis Rheumatol JT - Arthritis & rheumatology (Hoboken, N.J.) JID - 101623795 RN - 0 (Antibodies, Antinuclear) RN - 0 (Autoantibodies) RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Vaccines, DNA) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Antibodies, Antinuclear/*drug effects/immunology MH - Autoantibodies/*drug effects/immunology MH - DNA/immunology MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - HSP70 Heat-Shock Proteins/*pharmacology MH - Lupus Erythematosus, Systemic/immunology/*prevention & control MH - Mice MH - Mice, Inbred NZB MH - Vaccines, DNA/*pharmacology EDAT- 2020/01/17 06:00 MHDA- 2020/07/23 06:00 CRDT- 2020/01/17 06:00 PHST- 2019/07/15 00:00 [received] PHST- 2020/01/07 00:00 [accepted] PHST- 2020/01/17 06:00 [pubmed] PHST- 2020/07/23 06:00 [medline] PHST- 2020/01/17 06:00 [entrez] AID - 10.1002/art.41202 [doi] PST - ppublish SO - Arthritis Rheumatol. 2020 Jun;72(6):997-1002. doi: 10.1002/art.41202. Epub 2020 Apr 30.