CD4⁺ Foxp3⁺ regulatory T cell-mediated immunomodulation by anti-depressants inhibiting acid sphingomyelinase

References

Abdel Shakor, A.B., Atia, M.M., Kwiatkowska, K., and Sobota, A. (2012). Cell surface ceramide controls translocation of transferrin receptor to clathrin-coated pits. Cell Signal. 24, 677–684.10.1016/j.cellsig.2011.10.016Suche in Google Scholar PubMed

Albouz, S., Hauw, J.J., Berwald-Netter, Y., Boutry, J.M., Bourdon, R., and Baumann, N. (1981). Tricyclic antidepressants induce sphingomyelinase deficiency in fibroblast and neuroblastoma cell cultures. Biomedicine 35, 218–220.Suche in Google Scholar

Apostolidis, S.A., Rodriguez-Rodriguez, N., Suarez-Fueyo, A., Dioufa, N., Ozcan, E., Crispin, J.C., Tsokos, M.G., and Tsokos, G.C. (2016). Phosphatase PP2A is requisite for the function of regulatory T cells. Nat. Immunol. 17, 556–564.10.1038/ni.3390Suche in Google Scholar PubMed PubMed Central

Arenz, C. (2010). Small molecule inhibitors of acid sphingomyelinase. Cell Physiol. Biochem. 26, 1–8.10.1159/000315100Suche in Google Scholar PubMed

Avota, E., Gulbins, E., and Schneider-Schaulies, S. (2011). DC-SIGN mediated sphingomyelinase-activation and ceramide generation is essential for enhancement of viral uptake in dendritic cells. PLoS Pathog. 7, e1001290.10.1371/journal.ppat.1001290Suche in Google Scholar PubMed PubMed Central

Bai, A. and Guo, Y. (2017). Acid sphingomyelinase mediates human CD4⁺ T-cell signaling: potential roles in T-cell responses and diseases. Cell Death Dis. 8, e2963.10.1038/cddis.2017.360Suche in Google Scholar PubMed PubMed Central

Bai, A., Moss, A., Kokkotou, E., Usheva, A., Sun, X., Cheifetz, A., Zheng, Y., Longhi, M.S., Gao, W., Wu, Y., et al. (2014). CD39 and CD161 modulate Th17 responses in Crohn’s disease. J. Immunol. 193, 3366–3377.10.4049/jimmunol.1400346Suche in Google Scholar PubMed PubMed Central

Bai, A., Kokkotou, E., Zheng, Y., and Robson, S.C. (2015). Role of acid sphingomyelinase bioactivity in human CD4⁺ T-cell activation and immune responses. Cell Death Dis. 6, e1828.10.1038/cddis.2015.178Suche in Google Scholar PubMed PubMed Central

Beckmann, N., Sharma, D., Gulbins, E., Becker, K.A., and Edelmann, B. (2014). Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons. Front. Physiol. 5, 331.10.3389/fphys.2014.00331Suche in Google Scholar PubMed PubMed Central

Beyersdorf, N. and Muller, N. (2015). Sphingomyelin breakdown in T cells: role in activation, effector functions and immunoregulation. Biol. Chem. 396, 749–758.10.1515/hsz-2014-0282Suche in Google Scholar PubMed

Boucher, L.M., Wiegmann, K., Futterer, A., Pfeffer, K., Machleidt, T., Schutze, S., Mak, T.W., and Kronke, M. (1995). CD28 signals through acidic sphingomyelinase. J. Exp. Med. 181, 2059–2068.10.1084/jem.181.6.2059Suche in Google Scholar PubMed PubMed Central

Catalfamo, M., Tai, X., Karpova, T., McNally, J., and Henkart, P.A. (2008). TcR-induced regulated secretion leads to surface expression of CTLA-4 in CD4⁺ CD25⁺ T cells. Immunology 125, 70–79.10.1111/j.1365-2567.2008.02822.xSuche in Google Scholar PubMed PubMed Central

D’Cruz, L.M. and Klein, L. (2005). Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat. Immunol. 6, 1152–1159.10.1038/ni1264Suche in Google Scholar PubMed

Ferlinz, K., Hurwitz, R., Vielhaber, G., Suzuki, K., and Sandhoff, K. (1994). Occurrence of two molecular forms of human acid sphingomyelinase. Biochem. J. 301, 855–862.10.1042/bj3010855Suche in Google Scholar PubMed PubMed Central

Finnegan, C.M., Rawat, S.S., Cho, E.H., Guiffre, D.L., Lockett, S., Merrill, A.H., Jr., and Blumenthal, R. (2007). Sphingomyelinase restricts the lateral diffusion of CD4 and inhibits human immunodeficiency virus fusion. J. Virol. 81, 5294–5304.10.1128/JVI.02553-06Suche in Google Scholar PubMed PubMed Central

Fontenot, J.D., Rasmussen, J.P., Gavin, M.A., and Rudensky, A.Y. (2005). A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat. Immunol. 6, 1142–1151.10.1038/ni1263Suche in Google Scholar PubMed

Gabande-Rodriguez, E., Boya, P., Labrador, V., Dotti, C.G., and Ledesma, M.D. (2014). High sphingomyelin levels induce lysosomal damage and autophagy dysfunction in Niemann Pick disease type A. Cell Death Differ. 21, 864–875.10.1038/cdd.2014.4Suche in Google Scholar PubMed PubMed Central

Gallala, H.D. and Sandhoff, K. (2011). Biological function of the cellular lipid BMP-BMP as a key activator for cholesterol sorting and membrane digestion. Neurochem. Res. 36, 1594–1600.10.1007/s11064-010-0337-6Suche in Google Scholar PubMed

Gallala, H.D., Breiden, B., and Sandhoff, K. (2011). Regulation of the NPC2 protein-mediated cholesterol trafficking by membrane lipids. J. Neurochem. 116, 702–707.10.1111/j.1471-4159.2010.07014.xSuche in Google Scholar PubMed

Gassert, E., Avota, E., Harms, H., Krohne, G., Gulbins, E., and Schneider-Schaulies, S. (2009). Induction of membrane ceramides: a novel strategy to interfere with T lymphocyte cytoskeletal reorganisation in viral immunosuppression. PLoS Pathog. 5, e1000623.10.1371/journal.ppat.1000623Suche in Google Scholar PubMed PubMed Central

Gobin, V., Van Steendam, K., Fevery, S., Tilleman, K., Billiau, A.D., Denys, D., and Deforce, D.L. (2013). Fluoxetine reduces murine graft-versus-host disease by induction of T cell immunosuppression. J. Neuroimmune Pharmacol. 8, 934–943.10.1007/s11481-013-9463-7Suche in Google Scholar PubMed PubMed Central

Gobin, V., Van Steendam, K., Denys, D., and Deforce, D. (2014). Selective serotonin reuptake inhibitors as a novel class of immunosuppressants. Int. Immunopharmacol. 20, 148–156.10.1016/j.intimp.2014.02.030Suche in Google Scholar

Gogishvili, T., Luhder, F., Goebbels, S., Beer-Hammer, S., Pfeffer, K., and Hunig, T. (2013). Cell-intrinsic and -extrinsic control of Treg-cell homeostasis and function revealed by induced CD28 deletion. Eur. J. Immunol. 43, 188–193.10.1002/eji.201242824Suche in Google Scholar

Golovina, T.N., Mikheeva, T., Suhoski, M.M., Aqui, N.A., Tai, V.C., Shan, X., Liu, R., Balcarcel, R.R., Fisher, N., Levine, B.L., et al. (2008). CD28 costimulation is essential for human T regulatory expansion and function. J. Immunol. 181, 2855–2868.10.4049/jimmunol.181.4.2855Suche in Google Scholar

Grassme, H., Jekle, A., Riehle, A., Schwarz, H., Berger, J., Sandhoff, K., Kolesnick, R., and Gulbins, E. (2001). CD95 signaling via ceramide-rich membrane rafts. J. Biol. Chem. 276, 20589–20596.10.1074/jbc.M101207200Suche in Google Scholar

Grassme, H., Riehle, A., Wilker, B., and Gulbins, E. (2005). Rhinoviruses infect human epithelial cells via ceramide-enriched membrane platforms. J. Biol. Chem. 280, 26256–26262.10.1074/jbc.M500835200Suche in Google Scholar

Greber, U.F. (2016). Virus and host mechanics support membrane penetration and cell entry. J. Virol. 90, 3802–3805.10.1128/JVI.02568-15Suche in Google Scholar

Gulbins, E. and Kolesnick, R. (2002). Acid sphingomyelinase-derived ceramide signaling in apoptosis. Subcell. Biochem. 36, 229–244.10.1007/0-306-47931-1_12Suche in Google Scholar

Gulbins, E. and Kolesnick, R. (2003). Raft ceramide in molecular medicine. Oncogene 22, 7070–7077.10.1038/sj.onc.1207146Suche in Google Scholar

Gulbins, E., Bissonnette, R., Mahboubi, A., Martin, S., Nishioka, W., Brunner, T., Baier, G., Baier-Bitterlich, G., Byrd, C., Lang, F., et al. (1995). FAS-induced apoptosis is mediated via a ceramide-initiated RAS signaling pathway. Immunity 2, 341–351.10.1016/1074-7613(95)90142-6Suche in Google Scholar

Hannun, Y.A. and Obeid, L.M. (2008). Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell Biol. 9, 139–150.10.1038/nrm2329Suche in Google Scholar PubMed

Herz, J., Pardo, J., Kashkar, H., Schramm, M., Kuzmenkina, E., Bos, E., Wiegmann, K., Wallich, R., Peters, P.J., Herzig, S., et al. (2009). Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes. Nat. Immunol. 10, 761–768.10.1038/ni.1757Suche in Google Scholar

Himmerich, H., Milenovic, S., Fulda, S., Plumakers, B., Sheldrick, A.J., Michel, T.M., Kircher, T., and Rink, L. (2010). Regulatory T cells increased while IL-1β decreased during antidepressant therapy. J. Psychiatr. Res. 44, 1052–1057.10.1016/j.jpsychires.2010.03.005Suche in Google Scholar

Hollmann, C., Werner, S., Avota, E., Reuter, D., Japtok, L., Kleuser, B., Gulbins, E., Becker, K.A., Schneider-Schaulies, J., and Beyersdorf, N. (2016). Inhibition of acid sphingomyelinase allows for selective targeting of CD4⁺ conventional versus Foxp3⁺ regulatory T cells. J. Immunol. 197, 3130–3141.10.4049/jimmunol.1600691Suche in Google Scholar

Horinouchi, K., Erlich, S., Perl, D.P., Ferlinz, K., Bisgaier, C.L., Sandhoff, K., Desnick, R.J., Stewart, C.L., and Schuchman, E.H. (1995). Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease. Nat. Genet. 10, 288–293.10.1038/ng0795-288Suche in Google Scholar

Jin, L., Millard, A.C., Wuskell, J.P., Dong, X., Wu, D., Clark, H.A., and Loew, L.M. (2006). Characterization and application of a new optical probe for membrane lipid domains. Biophys. J. 90, 2563–2575.10.1529/biophysj.105.072884Suche in Google Scholar

Kolesnick, R.N., Goni, F.M., and Alonso, A. (2000). Compartmentalization of ceramide signaling: physical foundations and biological effects. J. Cell Physiol. 184, 285–300.10.1002/1097-4652(200009)184:3<285::AID-JCP2>3.0.CO;2-3Suche in Google Scholar

Kornhuber, J., Tripal, P., Reichel, M., Muhle, C., Rhein, C., Muehlbacher, M., Groemer, T.W., and Gulbins, E. (2010). Functional inhibitors of acid sphingomyelinase (FIASMAs): a novel pharmacological group of drugs with broad clinical applications. Cell Physiol. Biochem. 26, 9–20.10.1159/000315101Suche in Google Scholar

Kornhuber, J., Muehlbacher, M., Trapp, S., Pechmann, S., Friedl, A., Reichel, M., Muhle, C., Terfloth, L., Groemer, T.W., Spitzer, G.M., et al. (2011). Identification of novel functional inhibitors of acid sphingomyelinase. PLoS One 6, e23852.10.1371/journal.pone.0023852Suche in Google Scholar

Kornhuber, J., Muller, C.P., Becker, K.A., Reichel, M., and Gulbins, E. (2014). The ceramide system as a novel antidepressant target. Trends Pharmacol. Sci. 35, 293–304.10.1016/j.tips.2014.04.003Suche in Google Scholar

Levine, A.G., Arvey, A., Jin, W., and Rudensky, A.Y. (2014). Continuous requirement for the TCR in regulatory T cell function. Nat. Immunol. 15, 1070–1078.10.1038/ni.3004Suche in Google Scholar

Li, Y., Xiao, B., Qiu, W., Yang, L., Hu, B., Tian, X., and Yang, H. (2010). Altered expression of CD4⁺ CD25⁺ regulatory T cells and its 5-HT(1a) receptor in patients with major depression disorder. J. Affect. Disord. 124, 68–75.10.1016/j.jad.2009.10.018Suche in Google Scholar PubMed

Merkenschlager, M. and von Boehmer, H. (2010). PI3 kinase signalling blocks Foxp3 expression by sequestering Foxo factors. J. Exp. Med. 207, 1347–1350.10.1084/jem.20101156Suche in Google Scholar PubMed PubMed Central

Miguel, L., Owen, D.M., Lim, C., Liebig, C., Evans, J., Magee, A.I., and Jury, E.C. (2011). Primary human CD4⁺ T cells have diverse levels of membrane lipid order that correlate with their function. J. Immunol. 186, 3505–3516.10.4049/jimmunol.1002980Suche in Google Scholar PubMed

Moles, A., Tarrats, N., Fernandez-Checa, J.C., and Mari, M. (2012). Cathepsin B overexpression due to acid sphingomyelinase ablation promotes liver fibrosis in Niemann-Pick disease. J. Biol. Chem. 287, 1178–1188.10.1074/jbc.M111.272393Suche in Google Scholar PubMed PubMed Central

Mostert, J.P., Admiraal-Behloul, F., Hoogduin, J.M., Luyendijk, J., Heersema, D.J., van Buchem, M.A., and De Keyser, J. (2008). Effects of fluoxetine on disease activity in relapsing multiple sclerosis: a double-blind, placebo-controlled, exploratory study. J. Neurol. Neurosurg. Psychiatry 79, 1027–1031.10.1136/jnnp.2007.139345Suche in Google Scholar PubMed

Mueller, N., Avota, E., Collenburg, L., Grassme, H., and Schneider-Schaulies, S. (2014). Neutral sphingomyelinase in physiological and measles virus induced T cell suppression. PLoS Pathog. 10, e1004574.10.1371/journal.ppat.1004574Suche in Google Scholar PubMed PubMed Central

Ng, C.G., Coppens, I., Govindarajan, D., Pisciotta, J., Shulaev, V., and Griffin, D.E. (2008). Effect of host cell lipid metabolism on alphavirus replication, virion morphogenesis, and infectivity. Proc. Natl. Acad. Sci. USA 105, 16326–16331.10.1073/pnas.0808720105Suche in Google Scholar PubMed PubMed Central

O’Byrne, D. and Sansom, D. (2000). Lack of costimulation by both sphingomyelinase and C2 ceramide in resting human T cells. Immunology 100, 225–230.10.1046/j.1365-2567.2000.00030.xSuche in Google Scholar PubMed PubMed Central

Owen, D.M., Rentero, C., Magenau, A., Abu-Siniyeh, A., and Gaus, K. (2012). Quantitative imaging of membrane lipid order in cells and organisms. Nat. Protoc. 7, 24–35.10.1038/nprot.2011.419Suche in Google Scholar PubMed

Paterson, A.M., Lovitch, S.B., Sage, P.T., Juneja, V.R., Lee, Y., Trombley, J.D., Arancibia-Carcamo, C.V., Sobel, R.A., Rudensky, A.Y., Kuchroo, V.K., et al. (2015). Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity. J. Exp. Med. 212, 1603–1621.10.1084/jem.20141030Suche in Google Scholar PubMed PubMed Central

Qureshi, O.S., Zheng, Y., Nakamura, K., Attridge, K., Manzotti, C., Schmidt, E.M., Baker, J., Jeffery, L.E., Kaur, S., Briggs, Z., et al. (2011). Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 332, 600–603.10.1126/science.1202947Suche in Google Scholar PubMed PubMed Central

Reuter, D., Sparwasser, T., Hunig, T., and Schneider-Schaulies, J. (2012). Foxp3⁺ regulatory T cells control persistence of viral CNS infection. PLoS One 7, e33989.10.1371/journal.pone.0033989Suche in Google Scholar PubMed PubMed Central

Rook, G.A. and Lowry, C.A. (2008). The hygiene hypothesis and psychiatric disorders. Trends Immunol. 29, 150–158.10.1016/j.it.2008.01.002Suche in Google Scholar PubMed

Sauer, S., Bruno, L., Hertweck, A., Finlay, D., Leleu, M., Spivakov, M., Knight, Z.A., Cobb, B.S., Cantrell, D., O’Connor, E., et al. (2008). T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc. Natl. Acad. Sci. USA 105, 7797–7802.10.1073/pnas.0800928105Suche in Google Scholar PubMed PubMed Central

Schneider-Schaulies, J. and Schneider-Schaulies, S. (2013). Viral infections and sphingolipids. Handb. Exp. Pharmacol. 216, 321–340.10.1007/978-3-7091-1511-4_16Suche in Google Scholar PubMed

Schneider-Schaulies, J. and Schneider-Schaulies, S. (2015). Sphingolipids in viral infection. Biol. Chem. 396, 585–595.10.1007/978-3-7091-1511-4_16Suche in Google Scholar

Schubert, S., Moller-Ehrlich, K., Singethan, K., Wiese, S., Duprex, W.P., Rima, B.K., Niewiesk, S., and Schneider-Schaulies, J. (2006). A mouse model of persistent brain infection with recombinant Measles virus. J. Gen. Virol. 87, 2011–2019.10.1099/vir.0.81838-0Suche in Google Scholar PubMed

Schuchman, E.H. and Wasserstein, M.P. (2015). Types A and B Niemann-Pick disease. Best Pract. Res. Clin. Endocrinol. Metab. 29, 237–247.10.1016/j.beem.2014.10.002Suche in Google Scholar PubMed

Schuchman, E.H. and Desnick, R.J. (2017). Types A and B Niemann-Pick disease. Mol. Genet. Metab. 120, 27–33.10.1016/j.ymgme.2016.12.008Suche in Google Scholar PubMed PubMed Central

Smith, E.L. and Schuchman, E.H. (2008). The unexpected role of acid sphingomyelinase in cell death and the pathophysiology of common diseases. FASEB J. 22, 3419–3431.10.1096/fj.08-108043Suche in Google Scholar PubMed PubMed Central

Tani, H., Shiokawa, M., Kaname, Y., Kambara, H., Mori, Y., Abe, T., Moriishi, K., and Matsuura, Y. (2010). Involvement of ceramide in the propagation of Japanese encephalitis virus. J. Virol. 84, 2798–2807.10.1128/JVI.02499-09Suche in Google Scholar

Taniguchi, M., Ogiso, H., Takeuchi, T., Kitatani, K., Umehara, H., and Okazaki, T. (2015). Lysosomal ceramide generated by acid sphingomyelinase triggers cytosolic cathepsin B-mediated degradation of X-linked inhibitor of apoptosis protein in natural killer/T lymphoma cell apoptosis. Cell Death Dis. 6, e1717.10.1038/cddis.2015.82Suche in Google Scholar

Teichgraber, V., Ulrich, M., Endlich, N., Riethmuller, J., Wilker, B., De Oliveira-Munding, C.C., van Heeckeren, A.M., Barr, M.L., von Kurthy, G., Schmid, K.W., et al. (2008). Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat. Med. 14, 382–391.10.1038/nm1748Suche in Google Scholar

Tischner, D., Weishaupt, A., van den Brandt, J., Muller, N., Beyersdorf, N., Ip, C.W., Toyka, K.V., Hunig, T., Gold, R., Kerkau, T., et al. (2006). Polyclonal expansion of regulatory T cells interferes with effector cell migration in a model of multiple sclerosis. Brain 129, 2635–2647.10.1093/brain/awl213Suche in Google Scholar

Tischner, D., Theiss, J., Karabinskaya, A., van den Brandt, J., Reichardt, S.D., Karow, U., Herold, M.J., Luhder, F., Utermohlen, O., and Reichardt, H.M. (2011). Acid sphingomyelinase is required for protection of effector memory T cells against glucocorticoid-induced cell death. J. Immunol. 187, 4509–4516.10.4049/jimmunol.1100911Suche in Google Scholar

Tonnetti, L., Veri, M.C., Bonvini, E., and D’Adamio, L. (1999). A role for neutral sphingomyelinase-mediated ceramide production in T cell receptor-induced apoptosis and mitogen-activated protein kinase-mediated signal transduction. J. Exp. Med. 189, 1581–1589.10.1084/jem.189.10.1581Suche in Google Scholar

Veiga-Parga, T., Sehrawat, S., and Rouse, B.T. (2013). Role of regulatory T cells during virus infection. Immunol. Rev. 255, 182–196.10.1111/imr.12085Suche in Google Scholar

Voisset, C., Lavie, M., Helle, F., Op De Beeck, A., Bilheu, A., Bertrand-Michel, J., Terce, F., Cocquerel, L., Wychowski, C., Vu-Dac, N., et al. (2008). Ceramide enrichment of the plasma membrane induces CD81 internalization and inhibits hepatitis C virus entry. Cell Microbiol. 10, 606–617.10.1111/j.1462-5822.2007.01070.xSuche in Google Scholar

Walker, L.S. and Sansom, D.M. (2011). The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat. Rev. Immunol. 11, 852–863.10.1038/nri3108Suche in Google Scholar

Wiegmann, K., Schutze, S., Machleidt, T., Witte, D., and Kronke, M. (1994). Functional dichotomy of neutral and acidic sphingomyelinases in tumor necrosis factor signaling. Cell 78, 1005–1015.10.1016/0092-8674(94)90275-5Suche in Google Scholar

Xiong, Z.J., Huang, J., Poda, G., Pomes, R., and Prive, G.G. (2016). Structure of human acid sphingomyelinase reveals the role of the saposin domain in activating substrate hydrolysis. J. Mol. Biol. 428, 3026–3042.10.1016/j.jmb.2016.06.012Suche in Google Scholar PubMed

Yamaguchi, T., Wing, J.B., and Sakaguchi, S. (2011). Two modes of immune suppression by Foxp3⁺ regulatory T cells under inflammatory or non-inflammatory conditions. Semin. Immunol. 23, 424–430.10.1016/j.smim.2011.10.002Suche in Google Scholar PubMed

Yuan, X.Q., Qiu, G., Liu, X.J., Liu, S., Wu, Y., Wang, X., and Lu, T. (2012). Fluoxetine promotes remission in acute experimental autoimmune encephalomyelitis in rats. Neuroimmunomodulation 19, 201–208.10.1159/000334095Suche in Google Scholar PubMed

Zeiser, R., Leveson-Gower, D.B., Zambricki, E.A., Kambham, N., Beilhack, A., Loh, J., Hou, J.Z., and Negrin, R.S. (2008). Differential impact of mammalian target of rapamycin inhibition on CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells compared with conventional CD4⁺ T cells. Blood 111, 453–462.10.1182/blood-2007-06-094482Suche in Google Scholar PubMed PubMed Central

Zhang, W., Nie, L., Wang, Y., Wang, X.P., Zhao, H., Dongol, S., Maharjan, S., and Cheng, L. (2013a). CCL20 secretion from the nucleus pulposus improves the recruitment of CCR6-expressing Th17 cells to degenerated IVD tissues. PLoS One 8, e66286.10.1371/journal.pone.0066286Suche in Google Scholar PubMed PubMed Central

Zhang, Y., Zhen, H., Yao, W., Bian, F., Mao, X., Yang, X., and Jin, S. (2013b). Antidepressant drug, desipramine, alleviates allergic rhinitis by regulating Treg and Th17 cells. Int. J. Immunopathol. Pharmacol. 26, 107–115.10.1177/039463201302600110Suche in Google Scholar PubMed

Zhou, Y., Salker, M.S., Walker, B., Munzer, P., Borst, O., Gawaz, M., Gulbins, E., Singh, Y., and Lang, F. (2016). Acid sphingomyelinase (ASM) is a negative regulator of regulatory T cell (Treg) development. Cell Physiol. Biochem. 39, 985–995.10.1159/000447806Suche in Google Scholar PubMed

Zhu, J. and Shevach, E.M. (2014). TCR signaling fuels T(reg) cell suppressor function. Nat. Immunol. 15, 1002–1003.10.1038/ni.3014Suche in Google Scholar PubMed PubMed Central