Artículo

Alamino, V.A.; Montesinos, M.D.M.; Soler, M.F.; Giusiano, L.; Gigena, N.; Fozzatti, L.; Maller, S.M.; Méndez-Huergo, S.P.; Rabinovich, G.A.; Pellizas, C.G."Dendritic Cells Exposed to Triiodothyronine Deliver Pro-Inflammatory Signals and Amplify IL-17-Driven Immune Responses" (2019) Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 52(2):354-367
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

BACKGROUND/AIMS: Although a cross-talk between immune and endocrine systems has been well established, the precise pathways by which these signals co-regulate pro- and antiinflammatory responses on antigen-presenting cells remain poorly understood. In this work we investigated the mechanisms by which triiodothyronine (T3) controls T cell activity via dendritic cell (DC) modulation. METHODS: DCs from wild-type (WT) and IL-6-deficient mice were pulsed with T3. Cytokine production and programmed death protein ligands (PD-L) 1 and 2 expression were assayed by flow cytometry and ELISA. Interferon-regulatory factor-4 (IRF4) expression was evaluated by RT-qPCR and flow cytometry. The ability of DCs to stimulate allogenic splenocytes was assessed in a mixed lymphocyte reaction and the different profile markers were analyzed by flow cytometry and ELISA. For in vivo experiments, DCs treated with ovalbumin and T3 were injected into OTII mice. Proliferation, cytokine production, frequency of FoxP3+ regulatory T (Treg) cells and PD-1+ cells were determined by MTT assay, ELISA and flow cytometry, respectively. RESULTS: T3 endows DCs with pro-inflammatory potential capable of generating IL-17-dominant responses and down-modulating expression of PD-L1 and 2. T3-stimulated WT-DCs increased the proportion of IL-17-producing splenocytes, an effect which was eliminated when splenocytes were incubated with T3-treated DCs derived from IL-6-deficient mice. Enhanced IL-17 expression was recorded in both, CD4- and CD4+ populations and involved the IRF-4 pathway. Particularly, γδ-T cells but not natural killer (NK), NKT, B lymphocytes nor CD8+ T cells were the major source of IL-17-production from CD4- cells. Moreover, T3-conditioned DCs promoted a decrease of the FoxP3+ Treg population. Furthermore, T3 down-modulated PD-1 expression on CD4- cells thereby limiting inhibitory signals driven by this co-inhibitory pathway. Thus, T3 acts at the DC level to drive proinflammatory responses in vitro. Accordingly, we found that T3 induces IL-17 and IFNγ-dominant antigen-specific responses in vivo. CONCLUSION: These results emphasize the relevance of T3 as an additional immune-endocrine checkpoint and a novel therapeutic target to modulate IL-17-mediated pro-inflammatory responses. © Copyright by the Author(s). Published by Cell Physiol Biochem Press.

Registro:

Documento: Artículo
Título:Dendritic Cells Exposed to Triiodothyronine Deliver Pro-Inflammatory Signals and Amplify IL-17-Driven Immune Responses
Autor:Alamino, V.A.; Montesinos, M.D.M.; Soler, M.F.; Giusiano, L.; Gigena, N.; Fozzatti, L.; Maller, S.M.; Méndez-Huergo, S.P.; Rabinovich, G.A.; Pellizas, C.G.
Filiación:Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET) and Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de CórdobaCórdoba, Argentina
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME-CONICET) and Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos AiresBuenos Aires, Argentina
Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET) and Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de CórdobaCórdoba, Argentina
Palabras clave:Adaptive immunity; Dendritic cells; Pro-inflammatory signals; Th17; Triiodothyronine; γδ-T cells; Cd274 protein, mouse; interferon regulatory factor; interferon regulatory factor-4; interleukin 17; liothyronine; lymphocyte antigen receptor; Pdcd1lg2 protein, mouse; programmed death 1 ligand 1; programmed death 1 ligand 2; animal; CD4+ T lymphocyte; cell proliferation; dendritic cell; drug effect; gene expression regulation; genetics; immunology; inflammation; knockout mouse; mouse; natural killer cell; pathology; signal transduction; Animals; B7-H1 Antigen; CD4-Positive T-Lymphocytes; Cell Proliferation; Dendritic Cells; Gene Expression Regulation; Inflammation; Interferon Regulatory Factors; Interleukin-17; Killer Cells, Natural; Mice; Mice, Knockout; Programmed Cell Death 1 Ligand 2 Protein; Receptors, Antigen, T-Cell, gamma-delta; Signal Transduction; Triiodothyronine
Año:2019
Volumen:52
Número:2
Página de inicio:354
Página de fin:367
DOI: http://dx.doi.org/10.33594/000000025
Handle:http://hdl.handle.net/20.500.12110/paper_14219778_v52_n2_p354_Alamino
Título revista:Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Título revista abreviado:Cell. Physiol. Biochem.
ISSN:14219778
CAS:liothyronine, 6138-47-2, 6893-02-3; B7-H1 Antigen; Cd274 protein, mouse; interferon regulatory factor-4; Interferon Regulatory Factors; Interleukin-17; Pdcd1lg2 protein, mouse; Programmed Cell Death 1 Ligand 2 Protein; Receptors, Antigen, T-Cell, gamma-delta; Triiodothyronine
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14219778_v52_n2_p354_Alamino

Citas:

---------- APA ----------
Alamino, V.A., Montesinos, M.D.M., Soler, M.F., Giusiano, L., Gigena, N., Fozzatti, L., Maller, S.M.,..., Pellizas, C.G. (2019) . Dendritic Cells Exposed to Triiodothyronine Deliver Pro-Inflammatory Signals and Amplify IL-17-Driven Immune Responses. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 52(2), 354-367.
http://dx.doi.org/10.33594/000000025
---------- CHICAGO ----------
Alamino, V.A., Montesinos, M.D.M., Soler, M.F., Giusiano, L., Gigena, N., Fozzatti, L., et al. "Dendritic Cells Exposed to Triiodothyronine Deliver Pro-Inflammatory Signals and Amplify IL-17-Driven Immune Responses" . Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 52, no. 2 (2019) : 354-367.
http://dx.doi.org/10.33594/000000025
---------- MLA ----------
Alamino, V.A., Montesinos, M.D.M., Soler, M.F., Giusiano, L., Gigena, N., Fozzatti, L., et al. "Dendritic Cells Exposed to Triiodothyronine Deliver Pro-Inflammatory Signals and Amplify IL-17-Driven Immune Responses" . Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, vol. 52, no. 2, 2019, pp. 354-367.
http://dx.doi.org/10.33594/000000025
---------- VANCOUVER ----------
Alamino, V.A., Montesinos, M.D.M., Soler, M.F., Giusiano, L., Gigena, N., Fozzatti, L., et al. Dendritic Cells Exposed to Triiodothyronine Deliver Pro-Inflammatory Signals and Amplify IL-17-Driven Immune Responses. Cell. Physiol. Biochem. 2019;52(2):354-367.
http://dx.doi.org/10.33594/000000025