title: Altered Macrophage and Dendritic Cell Response inMif-/- Mice Reveals a Role of Mif for Inflammatory-Th1 Response in Type 1 Diabetes.
abstract: Macrophage migration inhibitory factor (Mif) is highly expressed in type 1 diabetes mellitus (T1DM). However, there is limited information about how Mif influences the activation of macrophages (Mφ) and dendritic cells (DC) in T1DM. To address this issue, we induced T1DM by administering multiple low doses of streptozotocin (STZ) toMif-/-or wild-type (Wt) BALB/c mice. We found thatMif-/-mice treated with STZ (Mif-/-STZ) developed lower levels of hyperglycemia, inflammatory cytokines, and specific pancreatic islet antigen- (PIAg-) IgG and displayed reduced cellular infiltration into the pancreatic islets compared to Wt mice treated with STZ (WtSTZ). Moreover, Mφand DC fromMif-/-STZ displayed lower expression of MHC-II, costimulatory molecules CD80, CD86, and CD40, Toll-like receptor- (TLR-) 2, and TLR-4 than WtSTZ. These changes were associated with a reduced capacity of Mφand DC fromMif-/-STZ to induce proliferation in ovalbumin-specific T cells. All the deficiencies observed inMif-/-STZ were recovered by exogenous administration of recombinant Mif. These findings suggest that Mif plays a role in the molecular mechanisms of Mφand DC activation and drives T cell responses involved in the pathology of T1DM. Therefore, Mif is a potential therapeutic target to reduce the pathology of T1DM.
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores (FES) Iztacala, Universidad Nacional Autónoma de México (UNAM), 54090 Tlalnepantla, MEX, Mexico.
authors.forename: Yuriko Itzel
authors.identifier: 0000-0002-0769-8523
authors.initials: YI
authors.lastname: Sánchez-Zamora
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores (FES) Iztacala, Universidad Nacional Autónoma de México (UNAM), 54090 Tlalnepantla, MEX, Mexico.
authors.forename: Imelda
authors.identifier: 0000-0002-0504-6812
authors.initials: I
authors.lastname: Juarez-Avelar
authors.affiliation: Carrera de Optometría, FES-Iztacala, UNAM, 54090 Tlalnepantla, MEX, Mexico.
authors.forename: Alicia
authors.initials: A
authors.lastname: Vazquez-Mendoza
authors.affiliation: Departamento de Neurodesarrollo y Fisiología, Instituto de Fisiología Celular, UNAM, 04510 Coyoacán, MEX, Mexico.
authors.forename: Marcia
authors.identifier: 0000-0001-5711-8868
authors.initials: M
authors.lastname: Hiriart
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores (FES) Iztacala, Universidad Nacional Autónoma de México (UNAM), 54090 Tlalnepantla, MEX, Mexico.
authors.forename: Miriam
authors.identifier: 0000-0003-2911-9390
authors.initials: M
authors.lastname: Rodriguez-Sosa
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D001786:Blood Glucose / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G; D007371:Interferon-gamma / Q000276:immunology; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000276:immunology; D007515:Islets of Langerhans / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D001323:Autoantibodies; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001786:Blood Glucose; D019013:CD40 Antigens; D007074:Immunoglobulin G; D008263:Macrophage Migration-Inhibitory Factors; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse