title: Monocytes from patients with type 1 diabetes spontaneously secrete proinflammatory cytokines inducing Th17 cells.
abstract: Autoimmune diseases including type 1 diabetes (T1D) are thought to have a Th1/Th17 bias. The underlying mechanisms driving the activation and differentiation of these proinflammatory T cells are unknown. We examined the monocytes isolated directly from the blood of T1D patients and found they spontaneously secreted the proinflammatory cytokines IL-1beta and IL-6, which are known to induce and expand Th17 cells. Moreover, these in vivo-activated monocytes from T1D subjects induced more IL-17-secreting cells from memory T cells compared with monocytes from healthy control subjects. The induction of IL-17-secreting T cells by monocytes from T1D subjects was reduced in vitro with a combination of an IL-6-blocking Ab and IL-1R antagonist. In this study, we report a significant although modest increase in the frequency of IL-17-secreting cells in lymphocytes from long-term patients with T1D compared with healthy controls. These data suggest that the innate immune system in T1D may drive the adaptive immune system by expanding the Th17 population of effector T cells.
authors.affiliation: Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Bradshaw
authors.forename: Khadir
authors.initials: K
authors.lastname: Raddassi
authors.forename: Wassim
authors.initials: W
authors.lastname: Elyaman
authors.forename: Tihamer
authors.initials: T
authors.lastname: Orban
authors.forename: Peter A
authors.initials: PA
authors.lastname: Gottlieb
authors.forename: Sally C
authors.initials: SC
authors.lastname: Kent
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002648:Child; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D018836:Inflammation Mediators / Q000097:blood / Q000502:physiology*; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D016207:Cytokines; C508600:IL6 protein, human; D018836:Inflammation Mediators; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6