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dc.contributor.authorSodré, Fernanda M. C.
dc.contributor.authorBissenova, Samal
dc.contributor.authorBruggeman, Ylke
dc.contributor.authorTilvawala, Ronak
dc.contributor.authorCook, Dana P.
dc.contributor.authorBerthault, Claire
dc.contributor.authorMondal, Santanu
dc.contributor.authorCallebaut, Aïsha
dc.contributor.authorYou, Sylvaine
dc.contributor.authorScharfmann, Raphael
dc.contributor.authorMallone, Roberto
dc.contributor.authorThompson, Paul R
dc.contributor.authorMathieu, Chantal
dc.contributor.authorBuitinga, Mijke
dc.contributor.authorOverbergh, Lut
dc.date2022-08-11T08:11:00.000
dc.date.accessioned2022-08-23T17:28:03Z
dc.date.available2022-08-23T17:28:03Z
dc.date.issued2020-11-17
dc.date.submitted2021-01-20
dc.identifier.citation<p>Sodré FMC, Bissenova S, Bruggeman Y, Tilvawala R, Cook DP, Berthault C, Mondal S, Callebaut A, You S, Scharfmann R, Mallone R, Thompson PR, Mathieu C, Buitinga M, Overbergh L. Peptidylarginine Deiminase Inhibition Prevents Diabetes Development in NOD Mice. Diabetes. 2020 Nov 17:db200421. doi: 10.2337/db20-0421. Epub ahead of print. PMID: 33203696. <a href="https://doi.org/10.2337/db20-0421" target="_blank" title="article on publisher's site">Link to article on publisher's site</a></p>
dc.identifier.issn1939-327X
dc.identifier.doi10.2337/db20-0421
dc.identifier.pmid33203696
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49999
dc.description.abstractProtein citrullination plays a role in several autoimmune diseases. Its involvement in murine and human type 1 diabetes has recently been recognized through the discovery of antibodies and T-cell reactivity against citrullinated peptides. In the current study, we demonstrate that systemic inhibition of peptidylarginine deiminases (PADs), the enzymes mediating citrullination, through BB-Cl-amidine treatment, prevents diabetes development in NOD mice. This prevention was associated with reduced levels of citrullination in the pancreas, decreased circulating autoantibody titers against citrullinated GRP78 and reduced spontaneous NETosis of bone marrow-derived neutrophils. Moreover, BB-Cl-amidine treatment induced a shift from Th1 to Th2 cytokines in the serum and an increase in the frequency of regulatory T cells in the blood and spleen. In the pancreas, BB-Cl-amidine treatment preserved insulin production and was associated with a less destructive immune infiltrate, characterized by reduced frequencies of effector memory CD4+ T cells and a modest reduction in the frequency of IFNγ-producing CD4+ and CD8+ T cells. Our results point to a role of citrullination in the pathogenesis of autoimmune diabetes, with PAD inhibition leading to disease prevention through modulation of immune pathways. These findings provide insight in the potential of PAD inhibition for treating autoimmune diseases like type 1 diabetes.
dc.language.isoen_US
dc.publisherAmerican Diabetes Association
dc.relation<p><a href="https://pubmed.ncbi.nlm.nih.gov/33203696/" target="_blank" title="article in PubMed">Article in PubMed</a></p>
dc.rights© 2020 by the American Diabetes Association https://www.diabetesjournals.org/content/license. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. Accepted manuscript posted as allowed by the publisher's self-archiving policy at https://www.diabetesjournals.org/content/ada-policies-and-procedures-peer-reviewed-publications?survey=1#acceptedmanuscripts.
dc.subjectType 1 diabetes
dc.subjectNOD mice
dc.subjectNeutrophils
dc.subjectPrevention
dc.subjectT Cells
dc.subjectProtein citrullination
dc.subjectBiochemistry
dc.subjectEndocrine System Diseases
dc.subjectEndocrinology, Diabetes, and Metabolism
dc.subjectEnzymes and Coenzymes
dc.subjectImmune System Diseases
dc.subjectMedicinal-Pharmaceutical Chemistry
dc.subjectNutritional and Metabolic Diseases
dc.subjectTherapeutics
dc.titlePeptidylarginine Deiminase Inhibition Prevents Diabetes Development in NOD Mice
dc.typeAccepted Manuscript
dc.source.journaltitleDiabetes
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1120&amp;context=thompson&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/thompson/118
dc.identifier.contextkey21181952
refterms.dateFOA2022-08-23T17:28:03Z
html.description.abstract<p>Protein citrullination plays a role in several autoimmune diseases. Its involvement in murine and human type 1 diabetes has recently been recognized through the discovery of antibodies and T-cell reactivity against citrullinated peptides. In the current study, we demonstrate that systemic inhibition of peptidylarginine deiminases (PADs), the enzymes mediating citrullination, through BB-Cl-amidine treatment, prevents diabetes development in NOD mice. This prevention was associated with reduced levels of citrullination in the pancreas, decreased circulating autoantibody titers against citrullinated GRP78 and reduced spontaneous NETosis of bone marrow-derived neutrophils. Moreover, BB-Cl-amidine treatment induced a shift from Th1 to Th2 cytokines in the serum and an increase in the frequency of regulatory T cells in the blood and spleen. In the pancreas, BB-Cl-amidine treatment preserved insulin production and was associated with a less destructive immune infiltrate, characterized by reduced frequencies of effector memory CD4+ T cells and a modest reduction in the frequency of IFNγ-producing CD4+ and CD8+ T cells. Our results point to a role of citrullination in the pathogenesis of autoimmune diabetes, with PAD inhibition leading to disease prevention through modulation of immune pathways. These findings provide insight in the potential of PAD inhibition for treating autoimmune diseases like type 1 diabetes.</p>
dc.identifier.submissionpaththompson/118
dc.contributor.departmentThompson Lab
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology


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