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Abstract:

Glucocorticoids are lipid-soluble hormones that signal via the glucocorticoid receptor (GR), a ligand-dependent transcription factor. Circulating glucocorticoids derive from the adrenals, but it is now apparent that paracrine glucocorticoid signaling occurs in multiple tissues. Effective local glucocorticoid concentrations and whether glucocorticoid delivery can be targeted to specific cell subsets are unknown. We use fluorescence detection of chromatin-associated GRs as biosensors of ligand binding and observe signals corresponding to steroid concentrations over physiological ranges in vitro and in vivo. In the thymus, where thymic epithelial cell (TEC)-synthesized glucocorticoids antagonize negative selection, we find that CD4 + CD8 + TCR hi cells, a small subset responding to self-antigens and undergoing selection, are specific targets of TEC-derived glucocorticoids and are exposed to 3-fold higher levels than other cells. These results demonstrate and quantitate targeted delivery of paracrine glucocorticoids. This approach may be used to assess in situ nuclear receptor signaling in a variety of physiological and pathological contexts. Glucocorticoids signal via the GR, a ligand-dependent transcription factor, and paracrine glucocorticoid signaling occurs in the thymus. Taves et al. use chromatin-associated GRs as biosensors to estimate glucocorticoid concentrations in vitro and in vivo. In the thymus, antigen-signaled CD4 + 8 + TCR hi cells are targeted by epithelial cell-synthesized glucocorticoids to promote positive selection. © 2019

Registro:

Documento: Artículo
Título:Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus
Autor:Taves, M.D.; Mittelstadt, P.R.; Presman, D.M.; Hager, G.L.; Ashwell, J.D.
Filiación:Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, United States
Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, United States
Instituto de Fisiología, Biología Molecular y Neurosciencias (IFIBYNE-UBA-CONICET), Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina
Palabras clave:Cyp11b1; glucocorticoid receptor; glucocorticoids; lymphocytes; nuclear receptors; paracrine; steroidogenesis; steroids; transcription factor
Año:2019
Volumen:26
Número:13
Página de inicio:3629
Página de fin:3642.e4
DOI: http://dx.doi.org/10.1016/j.celrep.2019.02.108
Título revista:Cell Reports
Título revista abreviado:Cell Rep.
ISSN:22111247
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_22111247_v26_n13_p3629_Taves

Referencias:

  • Amateau, S.K., Alt, J.J., Stamps, C.L., McCarthy, M.M., Brain estradiol content in newborn rats: sex differences, regional heterogeneity, and possible de novo synthesis by the female telencephalon (2004) Endocrinology, 145, pp. 2906-2917
  • Attardi, B., Ohno, S., Androgen and estrogen receptors in the developing mouse brain (1976) Endocrinology, 99, pp. 1279-1290
  • Baldwin, T.A., Hogquist, K.A., Transcriptional analysis of clonal deletion in vivo (2007) J. Immunol., 179, pp. 837-844
  • Blank, C., Brown, I., Marks, R., Nishimura, H., Honjo, T., Gajewski, T.F., Absence of programmed death receptor 1 alters thymic development and enhances generation of CD4/CD8 double-negative TCR-transgenic T cells (2003) J. Immunol., 171, pp. 4574-4581
  • Brewer, J.A., Sleckman, B.P., Swat, W., Muglia, L.J., Green fluorescent protein-glucocorticoid receptor knockin mice reveal dynamic receptor modulation during thymocyte development (2002) J. Immunol., 169, pp. 1309-1318
  • Buttgereit, F., Burmester, G.R., Lipworth, B.J., Optimised glucocorticoid therapy: the sharpening of an old spear (2005) Lancet, 365, pp. 801-803
  • Cima, I., Corazza, N., Dick, B., Fuhrer, A., Herren, S., Jakob, S., Ayuni, E., Brunner, T., Intestinal epithelial cells synthesize glucocorticoids and regulate T cell activation (2004) J. Exp. Med., 200, pp. 1635-1646
  • Cobice, D.F., Mackay, C.L., Goodwin, R.J.A., McBride, A., Langridge-Smith, P.R., Webster, S.P., Walker, B.R., Andrew, R., Mass spectrometry imaging for dissecting steroid intracrinology within target tissues (2013) Anal. Chem., 85, pp. 11576-11584
  • Croft, A.P., O'Callaghan, M.J., Shaw, S.G., Connolly, G., Jacquot, C., Little, H.J., Effects of minor laboratory procedures, adrenalectomy, social defeat or acute alcohol on regional brain concentrations of corticosterone (2008) Brain Res., 1238, pp. 12-22
  • Forment, J.V., Jackson, S.P., A flow cytometry-based method to simplify the analysis and quantification of protein association to chromatin in mammalian cells (2015) Nat. Protoc., 10, pp. 1297-1307
  • Giuliano, K.A., DeBiasio, R.L., Dunlay, R.T., Gough, A., Volosky, J.M., Zock, J., Pavlakis, G.N., Taylor, D.L., High-Content Screening: A New Approach to Easing Key Bottlenecks in the Drug Discovery Process (1997) J. Biomol. Screen., 2, pp. 249-259
  • Gray, D.H., Kupresanin, F., Berzins, S.P., Herold, M.J., O'Reilly, L.A., Bouillet, P., Strasser, A., The BH3-only proteins Bim and Puma cooperate to impose deletional tolerance of organ-specific antigens (2012) Immunity, 37, pp. 451-462
  • Ha, T., Kozlov, A.G., Lohman, T.M., Single-molecule views of protein movement on single-stranded DNA (2012) Annu. Rev. Biophys., 41, pp. 295-319
  • Hoffman, E.A., Frey, B.L., Smith, L.M., Auble, D.T., Formaldehyde crosslinking: a tool for the study of chromatin complexes (2015) J. Biol. Chem., 290, pp. 26404-26411
  • Htun, H., Holth, L.T., Walker, D., Davie, J.R., Hager, G.L., Direct visualization of the human estrogen receptor alpha reveals a role for ligand in the nuclear distribution of the receptor (1999) Mol. Biol. Cell, 10, pp. 471-486
  • Kearse, K.P., Takahama, Y., Punt, J.A., Sharrow, S.O., Singer, A., Early molecular events induced by T cell receptor (TCR) signaling in immature CD4+ CD8+ thymocytes: increased synthesis of TCR-alpha protein is an early response to TCR signaling that compensates for TCR-alpha instability, improves TCR assembly, and parallels other indicators of positive selection (1995) J. Exp. Med., 181, pp. 193-202
  • Lechner, O., Wiegers, G.J., Oliveira-Dos-Santos, A.J., Dietrich, H., Recheis, H., Waterman, M., Boyd, R., Wick, G., Glucocorticoid production in the murine thymus (2000) Eur. J. Immunol., 30, pp. 337-346
  • Liu, J., DeFranco, D.B., Protracted nuclear export of glucocorticoid receptor limits its turnover and does not require the exportin 1/CRM1-directed nuclear export pathway (2000) Mol. Endocrinol., 14, pp. 40-51
  • Mittelstadt, P.R., Monteiro, J.P., Ashwell, J.D., Thymocyte responsiveness to endogenous glucocorticoids is required for immunological fitness (2012) J. Clin. Invest., 122, pp. 2384-2394
  • Mittelstadt, P.R., Taves, M.D., Ashwell, J.D., Cutting Edge: De Novo Glucocorticoid Synthesis by Thymic Epithelial Cells Regulates Antigen-Specific Thymocyte Selection (2018) J. Immunol., 200, pp. 1988-1994
  • Mochizuki, N., Yamashita, S., Kurokawa, K., Ohba, Y., Nagai, T., Miyawaki, A., Matsuda, M., Spatio-temporal images of growth-factor-induced activation of Ras and Rap1 (2001) Nature, 411, pp. 1065-1068
  • Munck, A., Brinck-Johnsen, T., Specific and nonspecific physicochemical interactions of glucocorticoids and related steroids with rat thymus cells in vitro (1968) J. Biol. Chem., 243, pp. 5556-5565
  • Noti, M., Sidler, D., Brunner, T., Extra-adrenal glucocorticoid synthesis in the intestinal epithelium: more than a drop in the ocean? (2009) Semin. Immunopathol., 31, pp. 237-248
  • Noti, M., Corazza, N., Mueller, C., Berger, B., Brunner, T., TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis (2010) J. Exp. Med., 207, pp. 1057-1066
  • Overk, C.R., Perez, S.E., Ma, C., Taves, M.D., Soma, K.K., Mufson, E.J., Sex steroid levels and AD-like pathology in 3xTgAD mice (2013) J. Neuroendocrinol., 25, pp. 131-144
  • Paakinaho, V., Presman, D.M., Ball, D.A., Johnson, T.A., Schiltz, R.L., Levitt, P., Mazza, D., Hager, G.L., Single-molecule analysis of steroid receptor and cofactor action in living cells (2017) Nat. Commun., 8, p. 15896
  • Philibert, D., Raynaud, J.P., Progesterone binding in the immature mouse and rat uterus (1973) Steroids, 22, pp. 89-98
  • Presman, D.M., Ogara, M.F., Stortz, M., Alvarez, L.D., Pooley, J.R., Schiltz, R.L., Grøntved, L., Ashwell, J.D., Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor (2014) PLoS Biol., 12, p. e1001813
  • Presman, D.M., Ganguly, S., Schiltz, R.L., Johnson, T.A., Karpova, T.S., Hager, G.L., DNA binding triggers tetramerization of the glucocorticoid receptor in live cells (2016) Proc. Natl. Acad. Sci. USA, 113, pp. 8236-8241
  • Prior, N.H., Heimovics, S.A., Soma, K.K., Effects of water restriction on reproductive physiology and affiliative behavior in an opportunistically-breeding and monogamous songbird, the zebra finch (2013) Horm. Behav., 63, pp. 462-474
  • Reul, J.M., de Kloet, E.R., Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation (1985) Endocrinology, 117, pp. 2505-2511
  • Russo-Marie, F., Paing, M., Duval, D., Involvement of glucocorticoid receptors in steroid-induced inhibition of prostaglandin secretion (1979) J. Biol. Chem., 254, pp. 8498-8504
  • Schmidt, K.L., Soma, K.K., Cortisol and corticosterone in the songbird immune and nervous systems: local vs. systemic levels during development (2008) Am. J. Physiol. Regul. Integr. Comp. Physiol., 295, pp. R103-R110
  • Slominski, A., Zbytek, B., Szczesniewski, A., Semak, I., Kaminski, J., Sweatman, T., Wortsman, J., CRH stimulation of corticosteroids production in melanocytes is mediated by ACTH (2005) Am. J. Physiol. Endocrinol. Metab., 288, pp. E701-E706
  • Stavreva, D.A., Wiench, M., John, S., Conway-Campbell, B.L., McKenna, M.A., Pooley, J.R., Johnson, T.A., Hager, G.L., Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription (2009) Nat. Cell Biol., 11, pp. 1093-1102
  • Taves, M.D., Gomez-Sanchez, C.E., Soma, K.K., Extra-adrenal glucocorticoids and mineralocorticoids: evidence for local synthesis, regulation, and function (2011) Am. J. Physiol. Endocrinol. Metab., 301, pp. E11-E24
  • Taves, M.D., Ma, C., Heimovics, S.A., Saldanha, C.J., Soma, K.K., Measurement of steroid concentrations in brain tissue: methodological considerations (2011) Front. Endocrinol. (Lausanne), 2, p. 39
  • Taves, M.D., Plumb, A.W., Sandkam, B.A., Ma, C., Van Der Gugten, J.G., Holmes, D.T., Close, D.A., Soma, K.K., Steroid profiling reveals widespread local regulation of glucocorticoid levels during mouse development (2015) Endocrinology, 156, pp. 511-522
  • Taves, M.D., Losie, J.A., Rahim, T., Schmidt, K.L., Sandkam, B.A., Ma, C., Silversides, F.G., Soma, K.K., Locally elevated cortisol in lymphoid organs of the developing zebra finch but not Japanese quail or chicken (2016) Dev. Comp. Immunol., 54, pp. 116-125
  • Taves, M.D., Plumb, A.W., Korol, A.M., Van Der Gugten, J.G., Holmes, D.T., Abraham, N., Soma, K.K., Lymphoid organs of neonatal and adult mice preferentially produce active glucocorticoids from metabolites, not precursors (2016) Brain Behav. Immun., 57, pp. 271-281
  • Thévenot, D.R., Toth, K., Durst, R.A., Wilson, G.S., Electrochemical biosensors: recommended definitions and classification (2001) Biosens. Bioelectron., 16, pp. 121-131
  • Tobiansky, D.J., Korol, A.M., Ma, C., Hamden, J.E., Jalabert, C., Tomm, R.J., Soma, K.K., Testosterone and corticosterone in the mesocorticolimbic system of male rats: effects of gonadectomy and caloric restriction (2018) Endocrinology, 159, pp. 450-464
  • Vacchio, M.S., Papadopoulos, V., Ashwell, J.D., Steroid production in the thymus: implications for thymocyte selection (1994) J. Exp. Med., 179, pp. 1835-1846
  • Van Engelenburg, S.B., Palmer, A.E., Fluorescent biosensors of protein function (2008) Curr. Opin. Chem. Biol., 12, pp. 60-65
  • Wang, Y., Botvinick, E.L., Zhao, Y., Berns, M.W., Usami, S., Tsien, R.Y., Chien, S., Visualizing the mechanical activation of Src (2005) Nature, 434, pp. 1040-1045
  • Wasner, G., Hennermann, I., Kratochwil, K., Ontogeny of mesenchymal androgen receptors in the embryonic mouse mammary gland (1983) Endocrinology, 113, pp. 1771-1780
  • Weikum, E.R., Knuesel, M.T., Ortlund, E.A., Yamamoto, K.R., Glucocorticoid receptor control of transcription: precision and plasticity via allostery (2017) Nat. Rev. Mol. Cell Biol., 18, pp. 159-174
  • Wiegers, G.J., Knoflach, M., Böck, G., Niederegger, H., Dietrich, H., Falus, A., Boyd, R., Wick, G., CD4(+)CD8(+)TCR(low) thymocytes express low levels of glucocorticoid receptors while being sensitive to glucocorticoid-induced apoptosis (2001) Eur. J. Immunol., 31, pp. 2293-2301
  • Yang, E., van Nimwegen, E., Zavolan, M., Rajewsky, N., Schroeder, M., Magnasco, M., Darnell, J.E., Jr., Decay rates of human mRNAs: correlation with functional characteristics and sequence attributes (2003) Genome Res., 13, pp. 1863-1872
  • Yeakley, J.M., Balasubramanian, K., Harrison, R.W., Comparison of glucocorticoid-receptor binding kinetics with predictions from a biomolecular model (1980) J. Biol. Chem., 255, pp. 4182-4188
  • Zhang, J., Wang, X., Cui, W., Wang, W., Zhang, H., Liu, L., Zhang, Z., Li, B., Visualization of caspase-3-like activity in cells using a genetically encoded fluorescent biosensor activated by protein cleavage (2013) Nat. Commun., 4, p. 2157

Citas:

---------- APA ----------
Taves, M.D., Mittelstadt, P.R., Presman, D.M., Hager, G.L. & Ashwell, J.D. (2019) . Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus. Cell Reports, 26(13), 3629-3642.e4.
http://dx.doi.org/10.1016/j.celrep.2019.02.108
---------- CHICAGO ----------
Taves, M.D., Mittelstadt, P.R., Presman, D.M., Hager, G.L., Ashwell, J.D. "Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus" . Cell Reports 26, no. 13 (2019) : 3629-3642.e4.
http://dx.doi.org/10.1016/j.celrep.2019.02.108
---------- MLA ----------
Taves, M.D., Mittelstadt, P.R., Presman, D.M., Hager, G.L., Ashwell, J.D. "Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus" . Cell Reports, vol. 26, no. 13, 2019, pp. 3629-3642.e4.
http://dx.doi.org/10.1016/j.celrep.2019.02.108
---------- VANCOUVER ----------
Taves, M.D., Mittelstadt, P.R., Presman, D.M., Hager, G.L., Ashwell, J.D. Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus. Cell Rep. 2019;26(13):3629-3642.e4.
http://dx.doi.org/10.1016/j.celrep.2019.02.108