title: CD4+ cell-derived interleukin-17 in a model of dysregulated, Borrelia-induced arthritis.
abstract: Lyme borreliosis, which is caused in the United States by the spirochete Borrelia burgdorferi, may manifest as different arrays of signs, symptoms and severities between infected individuals. Recent studies have indicated that particularly severe forms of Lyme borreliosis in humans are associated with an increased Th17 response. Here, we hypothesized that a murine model combining the dysregulated immune response of an environment lacking interleukin-10 (IL-10) with a robust T-cell-driven inflammatory response would reflect arthritis associated with the production of IL-17 by CD4+ cells. We demonstrate that IL-10 regulates the production of IL-17 by Borrelia-primed CD4+ cells early after interaction with Lyme spirochetes in vitro and that infection of Borrelia-primed mice with B. burgdorferi leads to significant production of IL-17 that contributes to the development of severe arthritis. These results extend our previous findings by demonstrating that a dysregulated adaptive immune response to Lyme spirochetes can contribute to severe, Th17-associated arthritis. These findings may lead to therapeutic measures for individuals with particularly severe symptoms of Lyme borreliosis.
authors.affiliation: Department of Biomedical Sciences, University of Wisconsin-Milwaukee, Milwaukee WI 53211, USA.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Hansen
authors.affiliation: Department of Biomedical Sciences, University of Wisconsin-Milwaukee, Milwaukee WI 53211, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Johnson
authors.affiliation: Wisconsin State Laboratory of Hygiene, University of Wisconsin-Madison, Madison, WI 53706, USA Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Schell
authors.affiliation: Department of Biomedical Sciences, University of Wisconsin-Milwaukee, Milwaukee WI 53211, USA nardelld@uwm.edu.
authors.forename: Dean T
authors.initials: DT
authors.lastname: Nardelli
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D001898:Borrelia / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D008193:Lyme Disease / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D020381:Interleukin-17; D016753:Interleukin-10
keywords: Borrelia burgdorferi; Lyme arthritis; Lyme disease; interleukin-10; interleukin-17