title: Dissecting thyroid hormone transport and metabolism in dendritic cells.
abstract: We reported thyroid hormone (TH) receptor expression in murine dendritic cells (DCs) and 3,5,3'-triiodothyronine (T3)-dependent stimulation of DC maturation and ability to develop a Th1-type adaptive response. Moreover, an increased DC capacity to promote antigen-specific cytotoxic T-cell activity, exploited in a DC-based antitumor vaccination protocol, was revealed. However, putative effects of the main circulating TH, l-thyroxine (T4) and the mechanisms of TH transport and metabolism at DC level, crucial events for TH action at target cell level, were not known. Herein, we show that T4did not reproduce those registered T3-dependent effects, finding that may reflect a homoeostatic control to prevent unspecific systemic activation of DCs. Besides, DCs express MCT10 and LAT2 TH transporters, and these cells mainly transport T3with a favored involvement of MCT10 as its inhibition almost prevented T3saturable uptake mechanism and reduced T3-induced IL-12 production. In turn, DCs express iodothyronine deiodonases type 2 and 3 (D2, D3) and exhibit both enzymatic activities with a prevalence towards TH inactivation. Moreover, T3increased MCT10 and LAT2 expression and T3efflux from DCs but not T3uptake, whereas it induced a robust induction of D3 with a parallel slight reduction in D2. These findings disclose pivotal events involved in the mechanism of action of THs on DCs, providing valuable tools for manipulating the immunogenic potential of these cells. Furthermore, they broaden the knowledge of the TH mechanism of action at the immune system network.
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET)Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Gigena
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET)Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Vanina A
authors.initials: VA
authors.lastname: Alamino
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET)Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: María Del Mar
authors.initials: MD
authors.lastname: Montesinos
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET)Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Magalí
authors.initials: M
authors.lastname: Nazar
authors.affiliation: Instituto de Biofísica Carlos Chagas FilhoUniversidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Rio de Janeiro, Brazil.
authors.forename: Ruy A
authors.initials: RA
authors.lastname: Louzada
authors.affiliation: Thyroid UnitEndocrinology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Simone M
authors.initials: SM
authors.lastname: Wajner
authors.affiliation: Thyroid UnitEndocrinology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Maia
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET)Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Masini-Repiso
authors.affiliation: Instituto de Biofísica Carlos Chagas FilhoUniversidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Rio de Janeiro, Brazil.
authors.forename: Denise P
authors.initials: DP
authors.lastname: Carvalho
authors.affiliation: Laboratorio de Neuroinmunomodulación y Oncología MolecularInstituto de Investigaciones Biomédicas (BIOMED-CONICET), Universidad Católica Argentina, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Graciela A
authors.initials: GA
authors.lastname: Cremaschi
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET)Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina claudia@fcq.unc.edu.ar.
authors.forename: Claudia G
authors.initials: CG
authors.lastname: Pellizas
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D007453:Iodide Peroxidase / Q000378:metabolism; D051379:Mice; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D007453:Iodide Peroxidase
keywords: TH mechanism of action; TH metabolism; TH transport; dendritic cells (DCs); thyroid hormones (THs); triiodothyronine (T3)