{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T20:19:11Z","timestamp":1789935551980,"version":"4.0.1"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T00:00:00Z","timestamp":1497916800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T00:00:00Z","timestamp":1497916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Interleukin-22 (IL-22) plays an important role in host immunity and tissue homeostasis in infectious and inflammatory diseases. However, the function and regulation of IL-22 in viral infection remain largely unknown. Here, we report that viral infection triggered early IL-22 production from the liver and lymphoid organs. \u03b3\u03b4 T cells are the main immune cells to produce IL-22 in the liver, a process mediated by the IL-23\/phosphoinositide 3-kinase (PI3K)\/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. In the presence of IL-23, IL-22 production is independent of aryl hydrocarbon receptor (AhR) signaling. In acute and persistent viral infections, IL-22 deficiency resulted in thymic and splenic hypertrophy, while excessive IL-22 induced atrophy in these lymphoid organs. Moreover, IL-22 deficiency enhanced T cell responses to promote viral clearance, but increased IL-22 <jats:italic>in vivo<\/jats:italic> decreased T cell numbers and functions in the liver and lymphoid tissues. Together, our findings reveal a significant effect of the IL-23\/PI3K\/mTORC1 axis on regulating IL-22 production and also identify a novel role of IL-22 in controlling antiviral T cell responses in the non-lymphoid and lymphoid organs during acute and persistent viral infections.<\/jats:p>","DOI":"10.1038\/s41598-017-04260-0","type":"journal-article","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T10:07:21Z","timestamp":1497434841000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A tightly regulated IL-22 response maintains immune functions and homeostasis in systemic viral infection"],"prefix":"10.1038","volume":"7","author":[{"given":"Panpan","family":"Yi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuejin","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denley Ming Kee","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuliang","family":"Jie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zakari","family":"Kwota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzi","family":"Cong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuegong","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaren","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,20]]},"reference":[{"key":"4260_CR1","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1146\/annurev-immunol-032414-112123","volume":"33","author":"JA Dudakov","year":"2015","unstructured":"Dudakov, J. A., Hanash, A. M. & van den Brink, M. R. Interleukin-22: immunobiology and pathology. Annu Rev Immunol. \n                           33, 747\u2013785 (2015).","journal-title":"Annu Rev Immunol."},{"key":"4260_CR2","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1126\/science.aad9903","volume":"351","author":"R Duffin","year":"2016","unstructured":"Duffin, R. et al. Prostaglandin E(2) constrains systemic inflammation through an innate lymphoid cell-IL-22 axis. Science. \n                           351, 1333\u20131338 (2016).","journal-title":"Science."},{"key":"4260_CR3","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/ni.2025","volume":"12","author":"GF Sonnenberg","year":"2011","unstructured":"Sonnenberg, G. F., Fouser, L. A. & Artis, D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol. \n                           12, 383\u2013390 (2011).","journal-title":"Nat Immunol."},{"key":"4260_CR4","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1126\/science.1222551","volume":"336","author":"GF Sonnenberg","year":"2012","unstructured":"Sonnenberg, G. F. et al. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science. \n                           336, 1321\u20131325 (2012).","journal-title":"Science."},{"key":"4260_CR5","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1038\/ni1488","volume":"8","author":"L Zhou","year":"2007","unstructured":"Zhou, L. et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol. \n                           8, 967\u2013974 (2007).","journal-title":"Nat Immunol."},{"key":"4260_CR6","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1038\/nature05970","volume":"448","author":"T Korn","year":"2007","unstructured":"Korn, T. et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature. \n                           448, 484\u2013487 (2007).","journal-title":"Nature."},{"key":"4260_CR7","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.cell.2006.07.035","volume":"126","author":"II Ivanov","year":"2006","unstructured":"Ivanov, I. I. et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. \n                           126, 1121\u20131133 (2006).","journal-title":"Cell."},{"key":"4260_CR8","doi-asserted-by":"publisher","first-page":"3934","DOI":"10.4049\/jimmunol.1401234","volume":"193","author":"JJ Heller","year":"2014","unstructured":"Heller, J. J. et al. Restriction of IL-22-producing T cell responses and differential regulation of regulatory T cell compartments by zinc finger transcription factor Ikaros. J Immunol. \n                           193, 3934\u20133946 (2014).","journal-title":"J Immunol."},{"key":"4260_CR9","doi-asserted-by":"publisher","first-page":"8816","DOI":"10.1074\/jbc.M111.304758","volume":"287","author":"C Paget","year":"2012","unstructured":"Paget, C. et al. Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damages. J Biol Chem. \n                           287, 8816\u20138829 (2012).","journal-title":"J Biol Chem."},{"key":"4260_CR10","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/ni.2005","volume":"12","author":"GM Delgoffe","year":"2011","unstructured":"Delgoffe, G. M. et al. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat Immunol. \n                           12, 295\u2013303 (2011).","journal-title":"Nat Immunol."},{"key":"4260_CR11","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nri3198","volume":"12","author":"H Chi","year":"2012","unstructured":"Chi, H. Regulation and function of mTOR signalling in T cell fate decisions. Nat Rev Immunol. \n                           12, 325\u2013338 (2012).","journal-title":"Nat Rev Immunol."},{"key":"4260_CR12","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1126\/science.1256999","volume":"346","author":"B Zhang","year":"2014","unstructured":"Zhang, B. et al. Viral infection. Prevention and cure of rotavirus infection via TLR5\/NLRC4-mediated production of IL-22 and IL-18. Science. \n                           346, 861\u2013865 (2014).","journal-title":"Science."},{"key":"4260_CR13","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/ni.3180","volume":"16","author":"PP Hernandez","year":"2015","unstructured":"Hernandez, P. P. et al. Interferon-lambda and interleukin 22 act synergistically for the induction of interferon-stimulated genes and control of rotavirus infection. Nat Immunol. \n                           16, 698\u2013707 (2015).","journal-title":"Nat Immunol."},{"key":"4260_CR14","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3389\/fimmu.2016.00211","volume":"7","author":"S Gimeno Brias","year":"2016","unstructured":"Gimeno Brias, S., Stack, G., Stacey, M. A., Redwood, A. J. & Humphreys, I. R. The Role of IL-22 in Viral Infections: Paradigms and Paradoxes. Front Immunol. \n                           7, 211 (2016).","journal-title":"Front Immunol."},{"key":"4260_CR15","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1002\/hep.24339","volume":"54","author":"O Park","year":"2011","unstructured":"Park, O. et al. In vivo consequences of liver-specific interleukin-22 expression in mice: Implications for human liver disease progression. Hepatology. \n                           54, 252\u2013261 (2011).","journal-title":"Hepatology."},{"key":"4260_CR16","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1053\/j.gastro.2011.06.051","volume":"141","author":"Y Zhang","year":"2011","unstructured":"Zhang, Y. et al. A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus. Gastroenterology. \n                           141, 1897\u20131906 (2011).","journal-title":"Gastroenterology."},{"key":"4260_CR17","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1002\/hep.26916","volume":"59","author":"J Zhao","year":"2014","unstructured":"Zhao, J. et al. Pathological functions of interleukin-22 in chronic liver inflammation and fibrosis with hepatitis B virus infection by promoting T helper 17 cell recruitment. Hepatology. \n                           59, 1331\u20131342 (2014).","journal-title":"Hepatology."},{"key":"4260_CR18","doi-asserted-by":"publisher","first-page":"5531","DOI":"10.4049\/jimmunol.0904091","volume":"185","author":"SC Liang","year":"2010","unstructured":"Liang, S. C. et al. IL-22 induces an acute-phase response. J Immunol. \n                           185, 5531\u20135538 (2010).","journal-title":"J Immunol."},{"key":"4260_CR19","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.immuni.2010.12.009","volume":"34","author":"GF Sonnenberg","year":"2011","unstructured":"Sonnenberg, G. F., Monticelli, L. A., Elloso, M. M., Fouser, L. A. & Artis, D. CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity. \n                           34, 122\u2013134 (2011).","journal-title":"Immunity."},{"key":"4260_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000058829","volume":"79","author":"RL O\u2019Brien","year":"2001","unstructured":"O\u2019Brien, R. L., Lahn, M., Born, W. K. & Huber, S. A. T cell receptor and function cosegregate in gamma-delta T cell subsets. Chem Immunol. \n                           79, 1\u201328 (2001).","journal-title":"Chem Immunol."},{"key":"4260_CR21","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1189\/jlb.0703326","volume":"75","author":"CL Roark","year":"2004","unstructured":"Roark, C. L. et al. Subset-specific, uniform activation among V gamma 6\/V delta 1+ gamma delta T cells elicited by inflammation. J Leukoc Biol. \n                           75, 68\u201375 (2004).","journal-title":"J Leukoc Biol."},{"key":"4260_CR22","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/nrm3025","volume":"12","author":"R Zoncu","year":"2011","unstructured":"Zoncu, R., Efeyan, A. & Sabatini, D. M. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. \n                           12, 21\u201335 (2011).","journal-title":"Nat Rev Mol Cell Biol."},{"key":"4260_CR23","doi-asserted-by":"publisher","first-page":"5652","DOI":"10.4049\/jimmunol.176.9.5652","volume":"176","author":"ML Cho","year":"2006","unstructured":"Cho, M. L. et al. STAT3 and NF-kappaB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice. J Immunol. \n                           176, 5652\u20135661 (2006).","journal-title":"J Immunol."},{"key":"4260_CR24","doi-asserted-by":"publisher","first-page":"32493","DOI":"10.1074\/jbc.C300226200","volume":"278","author":"AF Castro","year":"2003","unstructured":"Castro, A. F., Rebhun, J. F., Clark, G. J. & Quilliam, L. A. Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner. J Biol Chem \n                           278, 32493\u201332496 (2003).","journal-title":"J Biol Chem"},{"key":"4260_CR25","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/S1097-2765(02)00568-3","volume":"10","author":"BD Manning","year":"2002","unstructured":"Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J. & Cantley, L. C. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase\/akt pathway. Mol Cell. \n                           10, 151\u2013162 (2002).","journal-title":"Mol Cell."},{"key":"4260_CR26","doi-asserted-by":"publisher","first-page":"13571","DOI":"10.1073\/pnas.202476899","volume":"99","author":"AR Tee","year":"2002","unstructured":"Tee, A. R. et al. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci USA \n                           99, 13571\u201313576 (2002).","journal-title":"Proc Natl Acad Sci USA"},{"key":"4260_CR27","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1093\/hmg\/11.5.525","volume":"11","author":"DJ Kwiatkowski","year":"2002","unstructured":"Kwiatkowski, D. J. et al. A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Hum Mol Genet \n                           11, 525\u2013534 (2002).","journal-title":"Hum Mol Genet"},{"key":"4260_CR28","doi-asserted-by":"publisher","first-page":"3753","DOI":"10.1038\/ncomms4753","volume":"5","author":"A Yeste","year":"2014","unstructured":"Yeste, A. et al. IL-21 induces IL-22 production in CD4+ T cells. Nat Commun. \n                           5, 3753 (2014).","journal-title":"Nat Commun."},{"key":"4260_CR29","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.immuni.2011.11.011","volume":"36","author":"J Qiu","year":"2012","unstructured":"Qiu, J. et al. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity. \n                           36, 92\u2013104 (2012).","journal-title":"Immunity."},{"key":"4260_CR30","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/ni.2035","volume":"12","author":"EJ Wherry","year":"2011","unstructured":"Wherry, E. J. T cell exhaustion. Nat Immunol. \n                           12, 492\u2013499 (2011).","journal-title":"Nat Immunol."},{"key":"4260_CR31","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.ajpath.2012.08.043","volume":"182","author":"MA Cobleigh","year":"2013","unstructured":"Cobleigh, M. A. & Robek, M. D. Protective and pathological properties of IL-22 in liver disease: implications for viral hepatitis. Am J Pathol \n                           182, 21\u201328 (2013).","journal-title":"Am J Pathol"},{"key":"4260_CR32","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.chom.2011.06.002","volume":"10","author":"AV Tumanov","year":"2011","unstructured":"Tumanov, A. V. et al. Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge. Cell Host Microbe \n                           10, 44\u201353 (2011).","journal-title":"Cell Host Microbe"},{"key":"4260_CR33","doi-asserted-by":"publisher","first-page":"4390","DOI":"10.4049\/jimmunol.1501541","volume":"196","author":"F Chen","year":"2016","unstructured":"Chen, F. et al. mTOR Mediates IL-23 Induction of Neutrophil IL-17 and IL-22 Production. J Immunol. \n                           196, 4390\u20134399 (2016).","journal-title":"J Immunol."},{"key":"4260_CR34","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.immuni.2011.12.011","volume":"36","author":"MA Kinnebrew","year":"2012","unstructured":"Kinnebrew, M. A. et al. Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity. \n                           36, 276\u2013287 (2012).","journal-title":"Immunity."},{"key":"4260_CR35","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/nri1573","volume":"5","author":"B Rehermann","year":"2005","unstructured":"Rehermann, B. & Nascimbeni, M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol \n                           5, 215\u2013229 (2005).","journal-title":"Nat Rev Immunol"},{"key":"4260_CR36","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1111\/j.1365-2893.2006.00723.x","volume":"13","author":"N Aslan","year":"2006","unstructured":"Aslan, N. et al. Cytotoxic CD4 T cells in viral hepatitis. J Viral Hepat \n                           13, 505\u2013514 (2006).","journal-title":"J Viral Hepat"},{"key":"4260_CR37","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1126\/science.1218004","volume":"336","author":"JA Dudakov","year":"2012","unstructured":"Dudakov, J. A. et al. Interleukin-22 drives endogenous thymic regeneration in mice. Science. \n                           336, 91\u201395 (2012).","journal-title":"Science."},{"key":"4260_CR38","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1002\/eji.201546241","volume":"46","author":"OB Corneth","year":"2016","unstructured":"Corneth, O. B. et al. Loss of IL-22 inhibits autoantibody formation in collagen-induced arthritis in mice. Eur J Immunol \n                           46, 1404\u20131414 (2016).","journal-title":"Eur J Immunol"},{"key":"4260_CR39","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1038\/ni.2112","volume":"12","author":"V Lukacs-Kornek","year":"2011","unstructured":"Lukacs-Kornek, V. et al. Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes. Nat Immunol. \n                           12, 1096\u20131104 (2011).","journal-title":"Nat Immunol."},{"key":"4260_CR40","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.virol.2010.02.022","volume":"401","author":"NE Pagliaccetti","year":"2010","unstructured":"Pagliaccetti, N. E., Chu, E. N., Bolen, C. R., Kleinstein, S. H. & Robek, M. D. Lambda and alpha interferons inhibit hepatitis B virus replication through a common molecular mechanism but with different in vivo activities. Virology. \n                           401, 197\u2013206 (2010).","journal-title":"Virology."},{"key":"4260_CR41","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.cyto.2007.11.016","volume":"41","author":"J Dambacher","year":"2008","unstructured":"Dambacher, J. et al. The role of interleukin-22 in hepatitis C virus infection. Cytokine. \n                           41, 209\u2013216 (2008).","journal-title":"Cytokine."},{"key":"4260_CR42","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1038\/35073658","volume":"410","author":"AJ McMichael","year":"2001","unstructured":"McMichael, A. J. & Rowland-Jones, S. L. Cellular immune responses to HIV. Nature. \n                           410, 980\u2013987 (2001).","journal-title":"Nature."},{"key":"4260_CR43","doi-asserted-by":"publisher","first-page":"4911","DOI":"10.1128\/JVI.77.8.4911-4927.2003","volume":"77","author":"EJ Wherry","year":"2003","unstructured":"Wherry, E. J., Blattman, J. N., Murali-Krishna, K., van der Most, R. & Ahmed, R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol. \n                           77, 4911\u20134927 (2003).","journal-title":"J Virol."},{"key":"4260_CR44","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1038\/ni1241","volume":"6","author":"P Klenerman","year":"2005","unstructured":"Klenerman, P. & Hill, A. T cells and viral persistence: lessons from diverse infections. Nat Immunol. \n                           6, 873\u2013879 (2005).","journal-title":"Nat Immunol."},{"key":"4260_CR45","doi-asserted-by":"publisher","first-page":"4215","DOI":"10.1128\/JVI.02844-06","volume":"81","author":"C Boni","year":"2007","unstructured":"Boni, C. et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J Virol. \n                           81, 4215\u20134225 (2007).","journal-title":"J Virol."},{"key":"4260_CR46","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.virol.2014.12.033","volume":"479\u2013480","author":"SM Kahan","year":"2015","unstructured":"Kahan, S. M., Wherry, E. J. & Zajac, A. J. T cell exhaustion during persistent viral infections. Virology. \n                           479\u2013480, 180\u2013193 (2015).","journal-title":"Virology."},{"key":"4260_CR47","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.cell.2011.01.011","volume":"144","author":"M Pellegrini","year":"2011","unstructured":"Pellegrini, M. et al. IL-7 engages multiple mechanisms to overcome chronic viral infection and limit organ pathology. Cell. \n                           144, 601\u2013613 (2011).","journal-title":"Cell."},{"key":"4260_CR48","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1182\/blood-2006-06-027912","volume":"109","author":"L Swainson","year":"2007","unstructured":"Swainson, L. et al. IL-7-induced proliferation of recent thymic emigrants requires activation of the PI3K pathway. Blood. \n                           109, 1034\u20131042 (2007).","journal-title":"Blood."},{"key":"4260_CR49","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.smim.2012.04.010","volume":"24","author":"F Carrette","year":"2012","unstructured":"Carrette, F. & Surh, C. D. IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasis. Semin Immunol. \n                           24, 209\u2013217 (2012).","journal-title":"Semin Immunol."},{"key":"4260_CR50","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/ni.3122","volume":"16","author":"A Boudil","year":"2015","unstructured":"Boudil, A. et al. IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte beta-selection. Nat Immunol. \n                           16, 397\u2013405 (2015).","journal-title":"Nat Immunol."},{"key":"4260_CR51","doi-asserted-by":"crossref","unstructured":"Welsh, R. M. & Seedhom, M. O. Lymphocytic choriomeningitis virus (LCMV): propagation, quantitation, and storage. Curr Protoc Microbiol. Chapter 15, Unit 15A 11 (2008).","DOI":"10.1002\/9780471729259.mc15a01s8"},{"key":"4260_CR52","doi-asserted-by":"publisher","first-page":"3052","DOI":"10.1002\/eji.201545696","volume":"45","author":"Y Liang","year":"2015","unstructured":"Liang, Y. et al. IL-33 promotes innate IFN-gamma production and modulates dendritic cell response in LCMV-induced hepatitis in mice. Eur J Immunol \n                           45, 3052\u20133063 (2015).","journal-title":"Eur J Immunol"},{"key":"4260_CR53","doi-asserted-by":"publisher","first-page":"621","DOI":"10.4049\/jimmunol.1201970","volume":"190","author":"L Hou","year":"2013","unstructured":"Hou, L. et al. Early IL-17 production by intrahepatic T cells is important for adaptive immune responses in viral hepatitis. J Immunol. \n                           190, 621\u2013629 (2013).","journal-title":"J Immunol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-04260-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-04260-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-04260-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T05:39:52Z","timestamp":1671773992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-04260-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,20]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["4260"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-04260-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,20]]},"assertion":[{"value":"2 February 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"3857"}}