title: IL-17-producing γδT cells are regulated by estrogen during development of experimental arthritis.
abstract: Interleukin-17 (IL-17) drives inflammation and destruction of joints in rheumatoid arthritis (RA). The female sex hormone 17β-estradiol (E2) inhibits experimental arthritis. γδT cells are significant producers of IL-17, thus the aim of this study was to investigate if E2 influenced IL-17(+) γδT cells during arthritis development using a variety of experimental RA models: collagen-induced arthritis (CIA); antigen-induced arthritis (AIA); and collagen antibody-induced arthritis (CAIA). We demonstrate that E2 treatment decreases IL-17(+) γδT cell number in joints, but increases IL-17(+) γδT cells in draining lymph nodes, suggesting an E2-mediated prevention of IL-17(+) γδT cell migration from lymph nodes to joints, in concert with our recently reported effects of E2 on Th17 cells (Andersson et al., 2015). E2 did neither influence the general γδT cell population nor IFNγ(+) γδT cells, implying a selective regulation of IL-17-producing cells. In conclusion, this study contributes to the understanding of estrogen's role in autoimmune disease.
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: annica.andersson@rheuma.gu.se.
authors.forename: Annica
authors.initials: A
authors.lastname: Andersson
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: louise.grahnemo@gu.se.
authors.forename: Louise
authors.initials: L
authors.lastname: Grahnemo
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden; Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: cecilia.engdahl@rheuma.gu.se.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Engdahl
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: alexandra.stubelius@rheuma.gu.se.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stubelius
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: marie.lagerquist@medic.gu.se.
authors.forename: Marie K
authors.initials: MK
authors.lastname: Lagerquist
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: hans.carlsten@rheuma.gu.se.
authors.forename: Hans
authors.initials: H
authors.lastname: Carlsten
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: ulrika.islander@rheuma.gu.se.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Islander
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D007596:Joints / Q000187:drug effects / Q000276:immunology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism; D054399:Receptors, CCR6 / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: C498126:CCR6 protein, mouse; D004967:Estrogens; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054399:Receptors, CCR6; D004958:Estradiol
keywords: Estrogen; Experimental arthritis; IL-17; Rheumatoid arthritis; γδT cells