Control of dendritic cell maturation and function by triiodothyronine.
Accumulating evidence indicates a functional crosstalk between immune and endocrine mechanisms in the modulation of innate and adaptive immunity. However, the impact of thyroid hormones (THs) in the initiation of adaptive immune responses has not yet been examined. Here we investigated the presence of thyroid hormone receptors (TRs) and the impact of THs in the physiology of mouse dendritic cells (DCs), specialized antigen-presenting cells with the unique capacity to fully activate naive T cells and orchestrate adaptive immunity. Both immature and lipopolysaccharide-matured bone marrow-derived DCs expressed TRs at mRNA and protein levels, showing a preferential cytoplasmic localization. Remarkably, physiological levels of triiodothyronine (T3) stimulated the expression of DC maturation markers (major histocompatibility complex II, CD80, CD86, and CD40), markedly increased the secretion of interleukin-12, and stimulated the ability of DCs to induce naive T cell proliferation and IFN-gamma production in allogeneic T cell cultures. Analysis of the mechanisms involved in these effects revealed the ability of T3 to influence the cytoplasmic-nuclear shuttling of nuclear factor-kappaB on primed DCs. Our study provides the first evidence for the presence of TRs on bone marrow-derived DCs and the ability of THs to regulate DC maturation and function. These results have profound implications in immunopathology, including cancer and autoimmune manifestations of the thyroid gland at the crossroads of the immune and endocrine systems.
Mascanfroni
Ivan
I
CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre esq. Medina Allende, Ciudad Universitaria, 5000 Córdoba, Argentina.
Montesinos
María del Mar
Mdel M
Susperreguy
Sebastián
S
Cervi
Laura
L
Ilarregui
Juan M
JM
Ramseyer
Vanesa D
VD
Masini-Repiso
Ana M
AM
Targovnik
Héctor M
HM
Rabinovich
Gabriel A
GA
Pellizas
Claudia G
CG
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D019556:COS Cells; D002454:Cell Differentiation; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000276:immunology; D051379:Mice; D011988:Receptors, Thyroid Hormone / Q000032:analysis / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology*
D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D018664:Interleukin-12