Fig. 1

1.Friedenstein, A. J., Chailakhyan, R. Ok., Latsinik, N. V., Panasyuk, A. F. & Keiliss-Borok, I. V. Stromal cells chargeable for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation
17, 331–340 (1974).2.Uccelli, A., Moretta, L. & Pistoia, V. Mesenchymal stem cells in well being and illness. Nat. Rev. Immunol.
eight, 726–736 (2008).Three.Bernardo, M. E. & Fibbe, W. E. Mesenchymal stromal cells: sensors and switchers of irritation. Cell Stem. Cell.
13, 392–402 (2013).four.Shi, Y., Su, J., Roberts, A. I., Shou, P., Rabson, A. B. & Ren, G. How mesenchymal stem cells work together with tissue immune responses. Tendencies Immunol.
33, 136–143 (2012).5.Shi, Y., Cao, J. & Wang, Y. Rethinking regeneration: empowerment of stem cells by irritation. Cell Loss of life Differ.
22, 1891–1892 (2015).6.Ren, G., Su, J., Zhang, L., Zhao, X., Ling, W. & L’Huillie, A. et al. Species variation within the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem Cells
27, 1954–1962 (2009).7.Su, J., Chen, X., Huang, Y., Li, W., Li, J. & Cao, Ok. et al. Phylogenetic distinction of iNOS and IDO perform in mesenchymal stem cell-mediated immunosuppression in mammalian species. Cell Loss of life Differ.
21, 388–396 (2014).eight.Hirata, F. & Hayaishi, O. Research on indoleamine 2,Three-dioxygenase. I. Superoxide anion as substrate. J. Biol. Chem.
250, 5960–5966 (1975).9.Munn, D. H. & Mellor, A. L. Indoleamine 2,Three dioxygenase and metabolic management of immune responses. Tendencies Immunol.
34, 137–143 (2013).10.Frumento, G., Rotondo, R., Tonetti, M., Damonte, G., Benatti, U. & Ferrara, G. B. Tryptophan-derived catabolites are chargeable for inhibition of T and pure killer cell proliferation induced by indoleamine 2,Three-dioxygenase. J. Exp. Med.
196, 459–468 (2002).11.Mezrich, J. D., Fechner, J. H., Zhang, X., Johnson, B. P., Burlingham, W. J. & Bradfield, C. A. An interplay between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J. Immunol.
185, 3190–3198 (2010).12.Yan, Y., Zhang, G. X., Gran, B., Fallarino, F., Yu, S. & Li, H. et al. IDO upregulates regulatory T cells through tryptophan catabolite and suppresses encephalitogenic T cell responses in experimental autoimmune encephalomyelitis. J. Immunol.
185, 5953–5961 (2010).13.DiNatale, B. C., Murray, I. A., Schroeder, J. C., Flaveny, C. A., Lahoti, T. S. & Laurenzana, E. M. et al. Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 within the presence of inflammatory signaling. Toxicol. Sci.
115, 89–97 (2010).14.Pallotta, M. T. et al. Indoleamine 2,Three-dioxygenase is a signaling protein in long-term tolerance by dendritic cells. Nat. Immunol.
12, 870–878 (2011).15.Choi, H., Lee, R. H., Bazhanov, N., Oh, J. Y. & Prockop, D. J. Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by reducing TLR2/NF-kappaB signaling in resident macrophages. Blood
118, 330–338 (2011).16.Danchuk, S., Ylostalo, J. H., Hossain, F., Sorge, R., Ramsey, A. & Bonvillain, R. W. et al. Human multipotent stromal cells attenuate lipopolysaccharide-induced acute lung damage in mice through secretion of tumor necrosis factor-alpha-induced protein 6. Stem Cell Res. Ther.
2, 27 (2011).17.Lee, R. H., Pulin, A. A., Web optimization, M. J., Kota, D. J., Ylostalo, J. & Larson, B. L. et al. Intravenous hMSCs enhance myocardial infarction in mice as a result of cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell.
5, 54–63 (2009).18.Oh, J. Y., Roddy, G. W., Choi, H., Lee, R. H., Ylostalo, J. H. & Rosa, R. H. Jr et al. Anti-inflammatory protein TSG-6 reduces inflammatory injury to the cornea following chemical and mechanical damage. Proc. Natl Acad. Sci. USA
107, 16875–16880 (2010).19.Milner, C. M. & Day, A. J. TSG-6: a multifunctional protein related to irritation. J. Cell Sci.
116, 1863–1873 (2003).20.Dyer, D. P., Thomson, J. M., Hermant, A., Jowitt, T. A., Handel, T. M. & Proudfoot, A. E. et al. TSG-6 inhibits neutrophil migration through direct interplay with the chemokine CXCL8. J. Immunol.
192, 2177–2185 (2014).21.Lesley, J., English, N. M., Gal, I., Mikecz, Ok., Day, A. J. & Hyman, R. Hyaluronan binding properties of a CD44 chimera containing the hyperlink module of TSG-6. J. Biol. Chem.
277, 26600–26608 (2002).22.Shi, Y., Hu, G., Su, J., Li, W., Chen, Q. & Shou, P. et al. Mesenchymal stem cells: a brand new technique for immunosuppression and tissue restore. Cell Res.
20, 510–518 (2010).23.Lee, J. W., Fang, X., Gupta, N., Serikov, V. & Matthay, M. A. Allogeneic human mesenchymal stem cells for remedy of E. coli endotoxin-induced acute lung damage within the ex vivo perfused human lung. Proc. Natl Acad. Sci. USA
106, 16357–16362 (2009).24.Mei, S. H., McCarter, S. D., Deng, Y., Parker, C. H., Liles, W. C. & Stewart, D. J. Prevention of LPS-induced acute lung damage in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Med.
four, e269 (2007).25.Ortiz, L. A., Dutreil, M., Fattman, C., Pandey, A. C., Torres, G. & Go, Ok. et al. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic impact of mesenchymal stem cells throughout lung damage. Proc. Natl Acad. Sci. USA
104, 11002–11007 (2007).26.Vecsei, L., Szalardy, L., Fulop, F. & Toldi, J. Kynurenines within the CNS: latest advances and new questions. Nat. Rev. Drug. Discov.
12, 64–82 (2013).27.Moroni, F., Cozzi, A., Sili, M. & Mannaioni, G. Kynurenic acid: a metabolite with a number of actions and a number of targets in mind and periphery. J. Neural. Transm.
119, 133–139 (2012).28.Murray, I. A., Patterson, A. D. & Perdew, G. H. Aryl hydrocarbon receptor ligands in most cancers: pal and foe. Nat. Rev. Most cancers
14, 801–814 (2014).29.Apetoh, L., Quintana, F. J., Pot, C., Joller, N., Xiao, S. & Kumar, D. et al. The aryl hydrocarbon receptor interacts with c-Maf to advertise the differentiation of sort 1 regulatory T cells induced by IL-27. Nat. Immunol.
11, 854–861 (2010).30.Stockinger, B., Di Meglio, P., Gialitakis, M. & Duarte, J. H. The aryl hydrocarbon receptor: multitasking within the immune system. Annu. Rev. Immunol.
32, 403–432 (2014).31.Metghalchi, S., Ponnuswamy, P., Simon, T., Haddad, Y., Laurans, L. & Clement, M. et al. Indoleamine 2,Three-dioxygenase fine-tunes immune homeostasis in atherosclerosis and colitis by way of repression of interleukin-10 manufacturing. Cell Metab.
22, 460–471 (2015).32.Pearce, E. L., Poffenberger, M. C., Chang, C. H. & Jones, R. G. Fueling immunity: insights into metabolism and lymphocyte perform. Science
342, 1242454 (2013).33.Grohmann, U., Bianchi, R., Belladonna, M. L., Silla, S., Fallarino, F. & Fioretti, M. C. et al. IFN-gamma inhibits presentation of a tumor/self peptide by CD8 alpha- dendritic cells through potentiation of the CD8 alpha+subset. J. Immunol.
165, 1357–1363 (2000).34.Hwu, P., Du, M. X., Lapointe, R., Do, M., Taylor, M. W. & Younger, H. A. Indoleamine 2,Three-dioxygenase manufacturing by human dendritic cells ends in the inhibition of T cell proliferation. J. Immunol.
164, 3596–3599 (2000).35.Munn, D. H., Shafizadeh, E., Attwood, J. T., Bondarev, I., Pashine, A. & Mellor, A. L. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J. Exp. Med.
189, 1363–1372 (1999).36.Schwarcz, R., Bruno, J. P., Muchowski, P. J. & Wu, H. Q. Kynurenines within the mammalian mind: when physiology meets pathology. Nat. Rev. Neurosci.
13, 465–477 (2012).37.Varga, G., Erces, D., Fazekas, B., Fulop, M., Kovacs, T. & Kaszaki, J. et al. N-Methyl-D-aspartate receptor antagonism decreases motility and inflammatory activation within the early section of acute experimental colitis within the rat. Neurogastroen Motil.
22, e268 (2010).38.Wang, J., Simonavicius, N., Wu, X., Swaminath, G., Reagan, J. & Tian, H. et al. Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. J. Biol. Chem.
281, 22021–22028 (2006).39.Ware, L. B. & Matthay, M. A. The acute respiratory misery syndrome. N. Engl. J. Med.
342, 1334–1349 (2000).40.Wheeler, A. P. & Bernard, G. R. Acute lung damage and the acute respiratory misery syndrome: a scientific overview. Lancet
369, 1553–1564 (2007).41.Wang, C. Y., Calfee, C. S., Paul, D. W., Janz, D. R., Could, A. Ok. & Zhuo, H. et al. One-year mortality and predictors of loss of life amongst hospital survivors of acute respiratory misery syndrome. Intens. Care Med.
40, 388–396 (2014).42.Horita, N., Hashimoto, S., Miyazawa, N., Fujita, H., Kojima, R. & Inoue, M. et al. Affect of corticosteroids on mortality in sufferers with acute respiratory misery syndrome: a scientific overview and meta-analysis. Inside Med.
54, 1473–1479 (2015).43.Iwata, Ok., Doi, A., Ohji, G., Oka, H., Oba, Y. & Takimoto, Ok. et al. Impact of neutrophil elastase inhibitor (sivelestat sodium) within the remedy of acute lung damage (ALI) and acute respiratory misery syndrome (ARDS): a scientific overview and meta-analysis. Inside Med.
49, 2423–2432 (2010).44.Anzueto, A., Baughman, R. P., Guntupalli, Ok. Ok., Weg, J. G., Wiedemann, H. P. & Raventos, A. A. et al. Aerosolized surfactant in adults with sepsis-induced acute respiratory misery syndrome. Exosurf Acute Respiratory Misery Syndrome Sepsis Examine Group. N. Engl. J. Med.
334, 1417–1421 (1996).45.Dellinger, R. P., Zimmerman, J. L., Taylor, R. W., Straube, R. C., Hauser, D. L. & Criner, G. J. et al. Results of inhaled nitric oxide in sufferers with acute respiratory misery syndrome: outcomes of a randomized section II trial. Inhaled Nitric Oxide in ARDS Examine Group. Crit. Care Med.
26, 15–23 (1998).46.Li, C., Bo, L., Liu, W., Lu, X. & Jin, F. Enteral immunomodulatory food regimen (omega-Three fatty acid, gamma-linolenic acid and antioxidant supplementation) for acute lung damage and acute respiratory misery syndrome: an up to date systematic overview and meta-analysis. Vitamins
7, 5572–5585 (2015).47.Nationwide Coronary heart, L., Blood Institute Acute Respiratory Misery Syndrome Scientific Trials N, Matthay, M. A., Brower, R. G., Carson, S. & Douglas, I. S. et al. Randomized, placebo-controlled scientific trial of an aerosolized beta(2)-agonist for remedy of acute lung damage. Am. J. Respir. Crit. Care Med.
184, 561–568 (2011).48.Nationwide Coronary heart L, Blood Institute ACTN, Truwit, J. D., Bernard, G. R., Steingrub, J. & Matthay, M. A. et al. Rosuvastatin for sepsis-associated acute respiratory misery syndrome. N. Engl. J. Med.
370, 2191–2200 (2014).49.Paine, R. third, Standiford, T. J., Dechert, R. E., Moss, M., Martin, G. S. & Rosenberg, A. L. et al. A randomized trial of recombinant human granulocyte-macrophage colony stimulating issue for sufferers with acute lung damage. Crit. Care Med.
40, 90–97 (2012).50.Matthay, M. A., Goolaerts, A., Howard, J. P. & Lee, J. W. Mesenchymal stem cells for acute lung damage: preclinical proof. Crit. Care Med.
38, S569–S573 (2010).51.Zheng, G., Huang, L., Tong, H., Shu, Q., Hu, Y. & Ge, M. et al. Remedy of acute respiratory misery syndrome with allogeneic adipose-derived mesenchymal stem cells: a randomized, placebo-controlled pilot research. Resp. Res.
15, 39 (2014).52.Ruitenberg, J. J., Mulder, C. B., Maino, V. C., Landay, A. L. & Ghanekar, S. A. VACUTAINER CPT and Ficoll density gradient separation carry out equivalently in sustaining the standard and performance of PBMC from HIV seropositive blood samples. BMC Immunol.
7, 11 (2006).53.Wilson, I. D., Nicholson, J. Ok., Castro-Perez, J., Granger, J. H., Johnson, Ok. A. & Smith, B. W. et al. Excessive decision “ultra performance” liquid chromatography coupled to oa-TOF mass spectrometry as a instrument for differential metabolic pathway profiling in practical genomic research. J. Proteome Res.
four, 591–598 (2005).


Please enter your comment!
Please enter your name here