title: Successful modulation of murine lupus nephritis with tuftsin-phosphorylcholine.
abstract: In areas where helminths infections are common, autoimmune diseases are rare. Treatment with helminths and ova from helminths, improved clinical findings of inflammatory bowel disease, multiple-sclerosis and rheumatoid-arthritis. The immunomodulatory functions of some helminths were attributed to the phosphorylcholine (PC) moiety. We aimed to decipher the tolerogenic potential of Tuftsin-PC (TPC) compound in mice genetically prone to develop lupus. Lupus prone NZBXW/F1 mice received subcutaneously TPC (5 μg/1 ml), 3 times a week starting at 14 weeks age. Autoantibodies were tested by ELISA, T-regulatory-cells by FACS, cytokines profile by RT-PCR and cytokines protein levels by DuoSet ELISA. Glomerulonephritis was addressed by detection of proteinuria, and immunoglobulin complex deposition in the mesangium of the kidneys of the mice by immunofluorescence. Our results show that TPC attenuated the development of glomerulonephritis in lupus prone mice, in particular, it ameliorated proteinuria (p < 0.02), and reduced immunoglobulin deposition in the kidney mesangium. TPC also enhanced the expression of TGFβ and IL-10 (p < 0.001), and inhibited the production of IFNγ and IL-17 (p < 0.03). TPC Significantly enhanced the expansion of CD4+CD25+FOXP3+ T-regulatory cells (Tregs) phenotype in the treated mice. These data indicate that TPC hampered lupus development in genetically lupus prone mice which was exemplified by moderate glomerulonephritis, attenuation of pro-inflammatory cytokines and enhancement of anti-inflammatory cytokines expression, as well as Tregs expansion. Our results propose harnessing novel natural therapy for lupus patients.
authors: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Tomer
authors: T
authors: Bashi
authors: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Miri
authors: M
authors: Blank
authors: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Dana
authors: D
authors: Ben-Ami Shor
authors: Department of Organic Chemistry, The Weizmann Institute of Sciences, Rehovot, Israel.
authors: Mati
authors: M
authors: Fridkin
authors: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Department of Internal Medicine, Archet-1 Hospital, University of Nice-Sophia-Antipolis, Nice, France.
authors: Mathilde
authors: M
authors: Versini
authors: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Omer
authors: O
authors: Gendelman
authors: Institute of Pathology, Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Alexander
authors: A
authors: Volkov
authors: Institute of Pathology, Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Iris
authors: I
authors: Barshak
authors: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Tel-Aviv University, Israel. Electronic address: shoenfel@post.tau.ac.il.
authors: Yehuda
authors: Y
authors: Shoenfeld
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000276:immunology; D005921:Glomerulonephritis / Q000188:drug therapy*; D006801:Humans; D007279:Injections, Subcutaneous; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008181:Lupus Nephritis / Q000188:drug therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008814:Mice, Inbred NZB; D010767:Phosphorylcholine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000138:chemical synthesis; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D014405:Tuftsin / Q000008:administration & dosage* / Q000138:chemical synthesis
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D010767:Phosphorylcholine; D014405:Tuftsin
keywords: Autoimmunity; Helminths; Lupus mice; Phosphorylcholine; Tuftsin