Artículo

Toscano, M.A.; Martínez Allo, V.C.; Cutine, A.M.; Rabinovich, G.A.; Mariño, K.V. "Untangling Galectin-Driven Regulatory Circuits in Autoimmune Inflammation" (2018) Trends in Molecular Medicine. 24(4):348-363
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Abstract:

Although progress has been made in understanding the mechanisms implicated in the pathogenesis of autoimmune inflammation, studies aimed at identifying the mediators of these pathways will be necessary to develop more selective therapies. Galectins, a family of glycan-binding proteins, play central roles in immune cell homeostasis. Whereas some members of this family trigger regulatory programs that promote resolution of inflammation, others contribute to perpetuate autoimmune processes. We discuss the roles of endogenous galectins and their specific glycosylated ligands in shaping autoimmune responses by fueling, extinguishing, or rewiring immune circuits. Understanding the relevance of galectin–glycan interactions in autoimmune inflammation could help to uncover novel pathways of tolerance breakdown, define molecular signatures for patient stratification and therapy responses, and open new avenues for immune intervention. © 2018 Elsevier Ltd

Registro:

Documento: Artículo
Título:Untangling Galectin-Driven Regulatory Circuits in Autoimmune Inflammation
Autor:Toscano, M.A.; Martínez Allo, V.C.; Cutine, A.M.; Rabinovich, G.A.; Mariño, K.V.
Filiación:Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, C1428, Argentina
Laboratorio de Glicómica Funcional y Molecular, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, C1428, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428, Argentina
Palabras clave:autoimmunity; chronic inflammation; galectins; glycans; immunoregulation; ecalectin; galectin; galectin 2; galectin 3; gamma interferon; glycan; interleukin 10; interleukin 17; interleukin 1beta; interleukin 27; tumor necrosis factor; biological factor; galectin; apoptosis; astrocyte; autoimmune disease; CD4+ T lymphocyte; CD8+ T lymphocyte; collagen-induced arthritis; Crohn disease; dendritic cell; endothelium cell; experimental autoimmune encephalomyelitis; glycosylation; human; immunocompetent cell; immunological tolerance; immunomodulation; inflammation; inflammatory bowel disease; insulin dependent diabetes mellitus; intestine flora; lymphocytic infiltration; macrophage; microglia; multiple sclerosis; nervous system inflammation; nonhuman; protein carbohydrate interaction; protein expression; protein function; regulatory T lymphocyte; Review; rheumatoid arthritis; systemic lupus erythematosus; Th1 cell; Th17 cell; ulcerative colitis; upregulation; adverse drug reaction; animal; autoimmune disease; autoimmunity; drug effect; inflammation; metabolism; Animals; Autoimmune Diseases; Autoimmunity; Biological Factors; Drug-Related Side Effects and Adverse Reactions; Galectins; Humans; Inflammation
Año:2018
Volumen:24
Número:4
Página de inicio:348
Página de fin:363
DOI: http://dx.doi.org/10.1016/j.molmed.2018.02.008
Título revista:Trends in Molecular Medicine
Título revista abreviado:Trends Mol. Med.
ISSN:14714914
CODEN:TMMRC
CAS:galectin 3, 208128-56-7; gamma interferon, 82115-62-6; Biological Factors; Galectins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14714914_v24_n4_p348_Toscano

Referencias:

  • Freitag, J., Immunometabolism and autoimmunity (2016) Immunol. Cell Biol., 94, pp. 925-934
  • Theofilopoulos, A.N., The multiple pathways to autoimmunity (2017) Nat. Immunol., 18, pp. 716-724
  • Caspi, R.R., Immunotherapy of autoimmunity and cancer: the penalty for success (2008) Nat. Rev. Immunol., 8, pp. 970-976
  • Cerliani, J.P., Translating the 'sugar code’ into immune and vascular signaling programs (2017) Trends Biochem. Sci., 42, pp. 255-273
  • Li, Y.J., A possible suppressive role of galectin-3 in upregulated osteoclastogenesis accompanying adjuvant-induced arthritis in rats (2009) Lab. Invest., 89, pp. 26-37
  • Stys, P.K., Will the real multiple sclerosis please stand up? (2012) Nat. Rev. Neurosci., 13, pp. 507-514
  • Stancic, M., Increased expression of distinct galectins in multiple sclerosis lesions (2011) Neuropathol. Appl. Neurobiol., 37, pp. 654-671
  • Toscano, M.A., Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death (2007) Nat. Immunol., 8, pp. 825-834
  • Ilarregui, J.M., Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10 (2009) Nat. Immunol., 10, pp. 981-991
  • Mari, E.R., Galectin-1 is essential for the induction of MOG35-55-based intravenous tolerance in experimental autoimmune encephalomyelitis (2016) Eur. J. Immunol., 46, pp. 1783-1796
  • Starossom, S.C., Galectin-1 deactivates classically activated microglia and protects from inflammation-induced neurodegeneration (2012) Immunity, 37, pp. 249-263
  • Zhu, C., The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity (2005) Nat. Immunol., 6, pp. 1245-1252
  • Oomizu, S., Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner (2012) Clin. Immunol., 143, pp. 51-58
  • Madireddi, S., Regulatory T cell-mediated suppression of inflammation induced by DR3 signaling is dependent on galectin-9 (2017) J. Immunol., 199, pp. 2721-2728
  • Steelman, A.J., Galectin-9 protein is up-regulated in astrocytes by tumor necrosis factor and promotes encephalitogenic T-cell apoptosis (2013) J. Biol. Chem., 288, pp. 23776-23787
  • Saresella, M., A role for the TIM-3/GAL-9/BAT3 pathway in determining the clinical phenotype of multiple sclerosis (2014) FASEB J., 28, pp. 5000-5009
  • Burman, J., Svenningsson, A., Cerebrospinal fluid concentration of Galectin-9 is increased in secondary progressive multiple sclerosis (2016) J. Neuroimmunol., 292, pp. 40-44
  • Jiang, H.R., Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis (2009) J. Immunol., 182, pp. 1167-1173
  • James, R.E., Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis (2016) Glia, 64, pp. 105-121
  • Jeon, S.B., Galectin-3 exerts cytokine-like regulatory actions through the JAK-STAT pathway (2010) J. Immunol., 185, pp. 7037-7046
  • Franco, P.G., Paving the way for adequate myelination: the contribution of galectin-3, transferrin and iron (2015) FEBS Lett., 589, pp. 3388-3395
  • Hoyos, H.C., Galectin-3 controls the response of microglial cells to limit cuprizone-induced demyelination (2014) Neurobiol. Dis., 62, pp. 441-455
  • Hoyos, H.C., The role of galectin-3: from oligodendroglial differentiation and myelination to demyelination and remyelination processes in a cuprizone-induced demyelination model (2016) Adv. Exp. Med. Biol., 949, pp. 311-332
  • Semerano, L., Novel immunotherapeutic avenues for rheumatoid arthritis (2016) Trends Mol. Med., 22, pp. 214-229
  • Rabinovich, G.A., Recombinant galectin-1 and its genetic delivery suppress collagen-induced arthritis via T cell apoptosis (1999) J. Exp. Med., 190, pp. 385-398
  • Iqbal, A.J., Endogenous galectin-1 exerts tonic inhibition on experimental arthritis (2013) J. Immunol., 191, pp. 171-177
  • Huang, Y.J., Multivalent structure of galectin-1–nanogold complex serves as potential therapeutics for rheumatoid arthritis by enhancing receptor clustering (2012) Eur. Cell Mater., 23, pp. 170-181
  • Wang, C.R., Intra-articular lentivirus-mediated delivery of galectin-3 shRNA and galectin-1 gene ameliorates collagen-induced arthritis (2010) Gene Ther., 17, pp. 1225-1233
  • Xibille-Friedmann, D., A decrease in galectin-1 (Gal-1) levels correlates with an increase in anti-Gal-1 antibodies at the synovial level in patients with rheumatoid arthritis (2013) Scand. J. Rheumatol., 42, pp. 102-107
  • Forsman, H., Galectin 3 aggravates joint inflammation and destruction in antigen-induced arthritis (2011) Arthritis Rheum., 63, pp. 445-454
  • Filer, A., Galectin 3 induces a distinctive pattern of cytokine and chemokine production in rheumatoid synovial fibroblasts via selective signaling pathways (2009) Arthritis Rheum., 60, pp. 1604-1614
  • Ezzat, M.H., Elevated production of galectin-3 is correlated with juvenile idiopathic arthritis disease activity, severity, and progression (2011) Int. J. Rheum. Dis., 14, pp. 345-352
  • Issa, S.F., Galectin-3 is persistently increased in early rheumatoid arthritis (RA) and associates with anti-CCP seropositivity and MRI bone lesions, while early fibrosis markers correlate with disease activity (2017) Scand. J. Immunol., 86, pp. 471-478
  • Issa, S.F., Increased galectin-3 may serve as a serologic signature of pre-rheumatoid arthritis while markers of synovitis and cartilage do not differ between early undifferentiated arthritis subsets (2017) Arthritis Res. Ther., 19, p. 80
  • Eshkar Sebban, L., The involvement of CD44 and its novel ligand galectin-8 in apoptotic regulation of autoimmune inflammation (2007) J. Immunol., 179, pp. 1225-1235
  • Pál, Z., Non-synonymous single nucleotide polymorphisms in genes for immunoregulatory galectins: association of galectin-8 (F19Y) occurrence with autoimmune diseases in a Caucasian population (2012) Biochim. Biophys. Acta, 1820, pp. 1512-1518
  • Seki, M., Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis of synovial fibroblasts (2007) Arthritis Rheum., 56, pp. 3968-3976
  • Lee, J., Underexpression of TIM-3 and blunted galectin-9-induced apoptosis of CD4+ T cells in rheumatoid arthritis (2012) Inflammation, 35, pp. 633-637
  • Seki, M., Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis (2008) Clin. Immunol., 127, pp. 78-88
  • Arikawa, T., Galectin-9 ameliorates immune complex-induced arthritis by regulating Fc gamma R expression on macrophages (2009) Clin. Immunol., 133, pp. 382-392
  • Atkinson, M.A., Type 1 diabetes (2014) Lancet, 383, pp. 69-82
  • Herold, K.C., Type 1 diabetes: translating mechanistic observations into effective clinical outcomes (2013) Nat. Rev. Immunol., 13, pp. 243-256
  • Perone, M.J., Suppression of autoimmune diabetes by soluble galectin-1 (2009) J. Immunol., 182, pp. 2641-2653
  • Wu, G., Ganglioside GM1 deficiency in effector T cells from NOD mice induces resistance to regulatory T-cell suppression (2011) Diabetes, 60, pp. 2341-2349
  • Gomez-Tourino, I., Galectin-1 synthesis in type 1 diabetes by different immune cell types: reduced synthesis by monocytes and Th1 cells (2011) Cell. Immunol., 271, pp. 319-328
  • Chou, F.C., Attenuation of Th1 response through galectin-9 and T-cell Ig mucin 3 interaction inhibits autoimmune diabetes in NOD mice (2009) Eur. J. Immunol., 39, pp. 2403-2411
  • Chou, F.C., Overexpression of galectin-9 in islets prolongs grafts survival via downregulation of Th1 responses (2013) Cell Transplant., 22, pp. 2135-2145
  • Kanzaki, M., Galectin-9 and T cell immunoglobulin mucin-3 pathway is a therapeutic target for type 1 diabetes (2012) Endocrinology, 153, pp. 612-620
  • Karlsen, A.E., Immune-mediated beta-cell destruction in vitro and in vivo – a pivotal role for galectin-3 (2006) Biochem. Biophys. Res. Commun., 344, pp. 406-415
  • Mensah-Brown, E.P., Targeted disruption of the galectin-3 gene results in decreased susceptibility to multiple low dose streptozotocin-induced diabetes in mice (2009) Clin. Immunol., 130, pp. 83-88
  • Saksida, T., Galectin-3 deficiency protects pancreatic islet cells from cytokine-triggered apoptosis in vitro (2013) J. Cell. Physiol., 228, pp. 1568-1576
  • Ordas, I., Ulcerative colitis (2012) Lancet, 380, pp. 1606-1619
  • Baumgart, D.C., Sandborn, W.J., Crohn's disease (2012) Lancet, 380, pp. 1590-1605
  • Block, M., Immunohistochemical studies on galectin expression in colectomised patients with ulcerative colitis (2016) BioMed Res. Int., 2016
  • Demetter, P., The galectin family and digestive disease (2008) J. Pathol., 215, pp. 1-12
  • Papa Gobbi, R., A galectin-specific signature in the gut delineates Crohn's disease and ulcerative colitis from other human inflammatory intestinal disorders (2016) Biofactors, 42, pp. 93-105
  • Tsai, H.F., Galectin-3 suppresses mucosal inflammation and reduces disease severity in experimental colitis (2016) J. Mol. Med., 94, pp. 545-556
  • Lippert, E., Galectin-3 modulates experimental colitis (2015) Digestion, 92, pp. 45-53
  • Simovic Markovic, B., Galectin-3 plays an important pro-inflammatory role in the induction phase of acute colitis by promoting activation of NLRP3 inflammasome and production of IL-1beta in macrophages (2016) J. Crohns Colitis, 10, pp. 593-606
  • Müller, S., Galectin-3 modulates T cell activity and is reduced in the inflamed intestinal epithelium in IBD (2006) Inflamm. Bowel Dis., 12, pp. 588-597
  • Lippert, E., Regulation of galectin-3 function in mucosal fibroblasts: potential role in mucosal inflammation (2008) Clin. Exp. Immunol., 152, pp. 285-297
  • Jensen-Jarolim, E., The constitutive expression of galectin-3 is downregulated in the intestinal epithelia of Crohn's disease patients, and tumour necrosis factor alpha decreases the level of galectin-3-specific mRNA in HCT-8 cells (2002) Eur. J. Gastroenterol. Hepatol., 14, pp. 145-152
  • Hokama, A., Induced reactivity of intestinal CD4+ T cells with an epithelial cell lectin, galectin-4, contributes to exacerbation of intestinal inflammation (2004) Immunity, 20, pp. 681-693
  • Nishida, A., Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells (2012) J. Exp. Med., 209, pp. 2383-2394
  • Paclik, D., Galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle (2008) PLoS One, 3
  • Paclik, D., Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice (2008) J. Mol. Med., 86, pp. 1395-1406
  • Santucci, L., Galectin-1 suppresses experimental colitis in mice (2003) Gastroenterology, 124, pp. 1381-1394
  • Muglia, C.I., Inflammation controls sensitivity of human and mouse intestinal epithelial cells to galectin-1 (2016) J. Cell. Physiol., 231, pp. 1575-1585
  • Moulton, V.R., Pathogenesis of human systemic lupus erythematosus: a cellular perspective (2017) Trends Mol. Med., 23, pp. 615-635
  • Liu, S.D., Galectin-1-induced down-regulation of T lymphocyte activation protects (NZB × NZW) F1 mice from lupus-like disease (2011) Lupus, 20, pp. 473-484
  • Moritoki, M., Galectin-9 ameliorates clinical severity of MRL/lpr lupus-prone mice by inducing plasma cell apoptosis independently of Tim-3 (2013) PLoS One, 8
  • Deak, M., Novel role for galectin-1 in T-cells under physiological and pathological conditions (2015) Immunobiology, 220, pp. 483-489
  • Shi, Z., The involvement of galectin -3 in skin injury in systemic lupus erythematosus patients (2017) Lupus, , https://doi.org/961203317736144, Published online October 23, 2017
  • Montiel, J.L., Anti-CD43 and anti-galectin-1 autoantibodies in patients with systemic lupus erythematosus (2010) Scand. J. Rheumatol., 39, pp. 50-57
  • Shi, Z.R., Association of anti-acidic ribosomal protein P0 and anti-galectin 3 antibodies with the development of skin lesions in systemic lupus erythematosus (2015) Arthritis Rheumatol., 67, pp. 193-203
  • Massardo, L., Autoantibodies against galectin-8: their specificity, association with lymphopenia in systemic lupus erythematosus and detection in rheumatoid arthritis and acute inflammation (2009) Lupus, 18, pp. 539-546
  • Vicuna, L., Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients (2013) Biol. Res., 46, pp. 275-280
  • Nabi, I.R., The galectin lattice at a glance (2015) Cell Sci., 128, pp. 2213-2219
  • Guardia, C.M., Structural basis of redox-dependent modulation of galectin-1 dynamics and function (2014) Glycobiology, 24, pp. 428-441
  • Hiramatsu, H., Involvement of histidine residues in the pH-dependent β-galactoside binding activity of human galectin-1 (2013) Biochemistry, 52, pp. 2371-2380
  • Rosenblum, M.D., Treating human autoimmunity: current practice and future prospects (2012) Sci. Transl. Med., 4
  • Vasta, G.R., Galectins as pattern recognition receptors: structure, function, and evolution (2012) Adv. Exp. Med. Biol., 946, pp. 21-36
  • Cagnoni, A.J., Turning-off signaling by siglecs, selectins, and galectins: chemical inhibition of glycan-dependent interactions in cancer (2016) Front. Oncol., 6, p. 109
  • Thiemann, S., Baum, L.G., Galectins and immune responses – just how do they do those things they do? (2016) Annu. Rev. Immunol., 34, pp. 243-264
  • Bonzi, J., Pre-B cell receptor binding to galectin-1 modifies galectin-1/carbohydrate affinity to modulate specific galectin-1/glycan lattice interactions (2015) Nat. Commun., 6
  • Nio-Kobayashi, J., Tissue- and cell-specific localization of galectins, beta-galactose-binding animal lectins, and their potential functions in health and disease (2017) Anat. Sci. Int., 92, pp. 25-36
  • Lee, S.U., N-glycan processing deficiency promotes spontaneous inflammatory demyelination and neurodegeneration (2007) J. Biol. Chem., 282, pp. 33725-33734
  • Green, R.S., Mammalian N-glycan branching protects against innate immune self-recognition and inflammation in autoimmune disease pathogenesis (2007) Immunity, 27, pp. 308-320
  • Togayachi, A., Polylactosamine on glycoproteins influences basal levels of lymphocyte and macrophage activation (2007) Proc. Natl. Acad. Sci. U. S. A., 104, pp. 15829-15834
  • Kudelka, M.R., Cosmc is an X-linked inflammatory bowel disease risk gene that spatially regulates gut microbiota and contributes to sex-specific risk (2016) Proc. Natl. Acad. Sci. U. S. A., 113, pp. 14787-14792
  • Commodaro, A.G., Autoimmune uveitis: the associated proinflammatory molecules and the search for immunoregulation (2011) Autoimmun. Rev., 10, pp. 205-209
  • Toscano, M.A., Galectin-1 suppresses autoimmune retinal disease by promoting concomitant Th2- and T regulatory-mediated anti-inflammatory responses (2006) J. Immunol., 176, pp. 6323-6332
  • Zanon Cde, F., Protective effects of the galectin-1 protein on in vivo and in vitro models of ocular inflammation (2015) Mol. Vis., 21, pp. 1036-1050
  • Romero, M.D., Circulating anti-galectin-1 antibodies are associated with the severity of ocular disease in autoimmune and infectious uveitis (2006) Invest. Ophthalmol. Vis. Sci., 47, pp. 1550-1556
  • Sampson, J.F., Galectin-8 ameliorates murine autoimmune ocular pathology and promotes a regulatory T cell response (2015) PLoS One, 10
  • Manns, M.P., Autoimmune hepatitis – update 2015 (2015) J. Hepatol., 62, pp. S100-S111
  • Santucci, L., Galectin-1 exerts immunomodulatory and protective effects on concanavalin A-induced hepatitis in mice (2000) Hepatology, 31, pp. 399-406
  • Lv, K., Galectin-9 ameliorates Con A-induced hepatitis by inducing CD4+CD25low/int effector T-cell apoptosis and increasing regulatory T cell number (2012) PLoS One, 7
  • Ju, Y., The Tim-3/galectin-9 pathway involves in the homeostasis of hepatic Tregs in a mouse model of concanavalin A-induced hepatitis (2014) Mol. Immunol., 58, pp. 85-91
  • Liberal, R., The impaired immune regulation of autoimmune hepatitis is linked to a defective galectin-9/tim-3 pathway (2012) Hepatology, 56, pp. 677-686
  • Volarevic, V., Galectin-3 deficiency prevents concanavalin A-induced hepatitis in mice (2012) Hepatology, 55, pp. 1954-1964
  • Volarevic, V., Gal-3 regulates the capacity of dendritic cells to promote NKT-cell-induced liver injury (2015) Eur. J. Immunol., 45, pp. 531-543
  • Silva, C.A., Diagnosis and classification of autoimmune orchitis (2014) Autoimmun. Rev., 13, pp. 431-434
  • Perez, C.V., Dual roles of endogenous and exogenous galectin-1 in the control of testicular immunopathology (2015) Sci. Rep., 5
  • McLachlan, S.M., Rapoport, B., Breaking tolerance to thyroid antigens: changing concepts in thyroid autoimmunity (2014) Endocr. Rev., 35, pp. 59-105
  • Leskela, S., Graves’ disease is associated with a defective expression of the immune regulatory molecule galectin-9 in antigen-presenting dendritic cells (2015) PLoS One, 10
  • Bellutti Enders, F., Correlation of CXCL10, tumor necrosis factor receptor type II, and galectin 9 with disease activity in juvenile dermatomyositis (2014) Arthritis Rheumatol., 66, pp. 2281-2289
  • Zhang, R., Increased levels of serum galectin-3 in patients with primary Sjögren's syndrome: associated with interstitial lung disease (2014) Cytokine, 69, pp. 289-293

Citas:

---------- APA ----------
Toscano, M.A., Martínez Allo, V.C., Cutine, A.M., Rabinovich, G.A. & Mariño, K.V. (2018) . Untangling Galectin-Driven Regulatory Circuits in Autoimmune Inflammation. Trends in Molecular Medicine, 24(4), 348-363.
http://dx.doi.org/10.1016/j.molmed.2018.02.008
---------- CHICAGO ----------
Toscano, M.A., Martínez Allo, V.C., Cutine, A.M., Rabinovich, G.A., Mariño, K.V. "Untangling Galectin-Driven Regulatory Circuits in Autoimmune Inflammation" . Trends in Molecular Medicine 24, no. 4 (2018) : 348-363.
http://dx.doi.org/10.1016/j.molmed.2018.02.008
---------- MLA ----------
Toscano, M.A., Martínez Allo, V.C., Cutine, A.M., Rabinovich, G.A., Mariño, K.V. "Untangling Galectin-Driven Regulatory Circuits in Autoimmune Inflammation" . Trends in Molecular Medicine, vol. 24, no. 4, 2018, pp. 348-363.
http://dx.doi.org/10.1016/j.molmed.2018.02.008
---------- VANCOUVER ----------
Toscano, M.A., Martínez Allo, V.C., Cutine, A.M., Rabinovich, G.A., Mariño, K.V. Untangling Galectin-Driven Regulatory Circuits in Autoimmune Inflammation. Trends Mol. Med. 2018;24(4):348-363.
http://dx.doi.org/10.1016/j.molmed.2018.02.008