title: A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis.
abstract: Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines. However, in both conditions, the reduction in clinical symptoms was associated with the absence of immune cell infiltrates in the target organ (islets and the brain tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide interacted with macrophages and reduced their capacity to secrete pro-inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of innate pro-inflammatory immune responses, which are central to the initiation of autoimmunity in both diseases, prevented the trafficking of autoreactive lymphocytes from the periphery to the site of autoimmunity (as opposed to directly modulating their function per se), and thus prevented tissue destruction. The ability of FhHDM-1 to modulate macrophage function, combined with its efficacy in disease prevention in multiple models, suggests that FhHDM-1 has considerable potential as a treatment for autoimmune diseases.
authors.affiliation: The School of Life Sciences, University of Technology Sydney, New South Wales, Australia.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Lund
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, Australia.
authors.forename: Judith
authors.initials: J
authors.lastname: Greer
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, Australia.
authors.forename: Aakanksha
authors.initials: A
authors.lastname: Dixit
authors.affiliation: The School of Life Sciences, University of Technology Sydney, New South Wales, Australia.
authors.forename: Raquel
authors.initials: R
authors.lastname: Alvarado
authors.affiliation: The School of Life Sciences, University of Technology Sydney, New South Wales, Australia.
authors.forename: Padraig
authors.initials: P
authors.lastname: McCauley-Winter
authors.affiliation: The School of Life Sciences, University of Technology Sydney, New South Wales, Australia.
authors.forename: Joyce
authors.initials: J
authors.lastname: To
authors.affiliation: The School of Life Sciences, University of Technology Sydney, New South Wales, Australia.
authors.forename: Akane
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: The School of Life Sciences, University of Technology Sydney, New South Wales, Australia.|The Centre for Health Technology, University of Technology Sydney, New South Wales, Australia.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hutchinson
authors.affiliation: Medical Biology Center, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, United Kingdom.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Robinson
authors.affiliation: The School of Life Sciences, University of Technology Sydney, New South Wales, Australia.|The Centre for Health Technology, University of Technology Sydney, New South Wales, Australia.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Simpson
authors.affiliation: The School of Life Sciences, University of Technology Sydney, New South Wales, Australia.|The Centre for Health Technology, University of Technology Sydney, New South Wales, Australia.
authors.forename: Bronwyn A
authors.initials: BA
authors.lastname: O'Brien
authors.affiliation: Medical Biology Center, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, United Kingdom.
authors.forename: John P
authors.initials: JP
authors.lastname: Dalton
authors.affiliation: The School of Life Sciences, University of Technology Sydney, New South Wales, Australia.
authors.forename: Sheila
authors.initials: S
authors.lastname: Donnelly
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D049109:Cell Proliferation / Q000502:physiology; D016207:Cytokines / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004195:Disease Models, Animal; D005210:Fasciola hepatica / Q000276:immunology; D005260:Female; D015801:Helminth Proteins / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009103:Multiple Sclerosis / Q000276:immunology*; D010271:Parasites / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; D015801:Helminth Proteins; D015850:Interleukin-6; D010455:Peptides