A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis
Lund, ME
Greer, J
Dixit, A
Alvarado, R
McCauley-Winter, P
To, J
Tanaka, A
Hutchinson, AT
Robinson, MW
Simpson, AM
O'Brien, BA
Dalton, JP
Donnelly, S
- Publication Type:
- Journal Article
- Citation:
- Scientific Reports, 2016, 6
- Issue Date:
- 2016-11-24
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author |
Lund, ME https://orcid.org/0000-0001-7360-5041 |
en_US |
dc.contributor.author | Greer, J | en_US |
dc.contributor.author | Dixit, A | en_US |
dc.contributor.author |
Alvarado, R https://orcid.org/0000-0001-7250-2200 |
en_US |
dc.contributor.author | McCauley-Winter, P | en_US |
dc.contributor.author |
To, J https://orcid.org/0000-0003-3482-4369 |
en_US |
dc.contributor.author |
Tanaka, A https://orcid.org/0000-0001-8851-7917 |
en_US |
dc.contributor.author | Hutchinson, AT | en_US |
dc.contributor.author |
Robinson, MW https://orcid.org/0000-0001-7191-0034 |
en_US |
dc.contributor.author |
Simpson, AM https://orcid.org/0000-0002-2249-5097 |
en_US |
dc.contributor.author |
O'Brien, BA https://orcid.org/0000-0001-5887-2424 |
en_US |
dc.contributor.author | Dalton, JP | en_US |
dc.contributor.author |
Donnelly, S https://orcid.org/0000-0003-2005-3698 |
en_US |
dc.date.available | 2016-11-02 | en_US |
dc.date.issued | 2016-11-24 | en_US |
dc.identifier.citation | Scientific Reports, 2016, 6 | en_US |
dc.identifier.uri | http://hdl.handle.net/10453/116021 | |
dc.description.abstract | © 2016 cThe Author(s). 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. | en_US |
dc.relation | http://purl.org/au-research/grants/nhmrc/GNT1087341 | |
dc.relation.ispartof | Scientific Reports | en_US |
dc.relation.isbasedon | 10.1038/srep37789 | en_US |
dc.subject.mesh | T-Lymphocytes | en_US |
dc.subject.mesh | Macrophages | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Mice, Inbred BALB C | en_US |
dc.subject.mesh | Mice | en_US |
dc.subject.mesh | Fasciola hepatica | en_US |
dc.subject.mesh | Parasites | en_US |
dc.subject.mesh | Multiple Sclerosis | en_US |
dc.subject.mesh | Diabetes Mellitus, Type 1 | en_US |
dc.subject.mesh | Autoimmune Diseases | en_US |
dc.subject.mesh | Disease Models, Animal | en_US |
dc.subject.mesh | Inflammation | en_US |
dc.subject.mesh | Peptides | en_US |
dc.subject.mesh | Helminth Proteins | en_US |
dc.subject.mesh | Interleukin-6 | en_US |
dc.subject.mesh | Cytokines | en_US |
dc.subject.mesh | Cell Proliferation | en_US |
dc.subject.mesh | Autoimmunity | en_US |
dc.subject.mesh | Female | en_US |
dc.title | A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis | en_US |
dc.type | Journal Article | |
utslib.citation.volume | 6 | en_US |
utslib.for | 0604 Genetics | en_US |
utslib.for | 1103 Clinical Sciences | en_US |
pubs.embargo.period | Not known | en_US |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Medical and Molecular Sciences | |
pubs.organisational-group | /University of Technology Sydney/Strength - CHT - Health Technologies | |
pubs.organisational-group | /University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation | |
utslib.copyright.status | open_access | |
pubs.publication-status | Published | en_US |
pubs.volume | 6 | en_US |
Abstract:
© 2016 cThe Author(s). 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.
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