{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:53:32Z","timestamp":1793840012037,"version":"4.6.1"},"reference-count":113,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070757, 81471530"],"award-info":[{"award-number":["82070757, 81471530"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Animal models play an indispensable role in the study of human diseases. However, animal models of different diseases do not fully mimic the complex internal environment of humans. Immunodeficient mice are deficient in certain genes and do not express these or show reduced expression in some of their cells, facilitating the establishment of humanized mice and simulation of the human environment\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Here, we summarize the developments in immunodeficient mice, from the initial nude mice lacking T lymphocytes to NOD\/SCID rg\n                    <jats:sup>null<\/jats:sup>\n                    mice lacking T, B, and NK cell populations. We describe existing humanized immune system mouse models based on immunodeficient mice in which human cells or tissues have been transplanted to establish a human immune system, including humanized-peripheral blood mononuclear cells (Hu-PBMCs), humanized hematopoietic stem cells (Hu-HSCs), and humanized bone marrow, liver, thymus (Hu-BLT) mouse models. The different methods for their development involve varying levels of complexity and humanization. Humanized mice are widely used in the study of various diseases to provide a transitional stage for clinical research. However, several challenges persist, including improving the efficiency of reconstructing the human B cell immune response, extending lifespan, improving the survival rate of mice to extend the observation period, and improving the development of standardized commercialized models and as well as their use. Overall, there are many opportunities and challenges in the development of humanized immune system mouse models which can provide novel strategies for understanding the mechanisms and treatments of human disease.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.1007579","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T13:22:54Z","timestamp":1666185774000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":172,"title":["The development and improvement of immunodeficient mice and humanized immune system mouse models"],"prefix":"10.3389","volume":"13","author":[{"given":"Jiaxuan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzhen","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengzhi","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanren","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangyuan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengbiao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-feng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingjun","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1017\/s0016672300010168","article-title":"'Nude', a new hairless gene with pleiotropic effects in the mouse","volume":"8","author":"Flanagan","year":"1966","journal-title":"Genetical Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90360-7","article-title":"Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation","volume":"80","author":"Blunt","year":"1995","journal-title":"Cell"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/301527a0","article-title":"A severe combined immunodeficiency mutation in the mouse","volume":"301","author":"Bosma","year":"1983","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.8.1965","article-title":"Molecular and biochemical characterisation of DNA-dependent protein kinase-defective rodent mutant irs-20","volume":"26","author":"Priestley","year":"1998","journal-title":"Nucleic Acids Res"},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.154.1.180","article-title":"Multiple defects in innate and adaptive immunologic function in NOD\/LtSz-scid mice","volume":"154","author":"Shultz","year":"1995","journal-title":"J Immunol (Baltimore Md. 1950)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.63.321","article-title":"NOD-Rag2null IL-2R\u03b3null mice: an alternative to NOG mice for generation of humanized mice","volume":"63","author":"Katano","year":"2014","journal-title":"Exp Anim"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1242\/dev.24.3.615","article-title":"Thymus dysgenesis in nude (nu nu) mice","volume":"24","author":"Pantelouris","year":"1970","journal-title":"J embryol Exp morphol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s0099-2399(06)80565-0","article-title":"Effect of T-cell deficiency on the formation of periapical lesions in mice: histological comparison between periapical lesion formation in BALB\/c and BALB\/c nu\/nu mice","volume":"21","author":"Tani","year":"1995","journal-title":"J endodontics"},{"key":"B9","article-title":"Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice","volume":"48","author":"Morikawa","year":"1988","journal-title":"Cancer Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1017\/s003118201600024x","article-title":"Distinct courses of infection with leishmania (L.) amazonensis are observed in BALB\/c, BALB\/c nude and C57BL\/6 mice","volume":"143","author":"Velasquez","year":"2016","journal-title":"Parasitology"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1159\/000232530","article-title":"Inability of intravenously injected monocellular suspensions of human bone marrow to establish in the nude mouse","volume":"62","author":"Ganick","year":"1980","journal-title":"Int Arch Allergy Appl Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00347.x","article-title":"Mouse models with human immunity and their application in biomedical research","volume":"13","author":"Zhang","year":"2009","journal-title":"J Cell Mol Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nri2017","article-title":"Humanized mice in translational biomedical research","volume":"7","author":"Shultz","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/stem.160166","article-title":"SCID mouse models of human stem cell engraftment","volume":"16","author":"Greiner","year":"1998","journal-title":"Stem Cells (Dayton Ohio)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90030-g","article-title":"RAG-1-deficient mice have no mature b and T lymphocytes","volume":"68","author":"Mombaerts","year":"1992","journal-title":"Cell"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.3.1016","article-title":"Evidence of functional lymphocytes in some (leaky) scid mice","volume":"167","author":"Bosma","year":"1988","journal-title":"J Exp Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90029-c","article-title":"RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement","volume":"68","author":"Shinkai","year":"1992","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/01.Tp.0000083041.44829.2c","article-title":"NOD\/LtSz-Rag1nullPfpnull mice: a new model system with increased levels of human peripheral leukocyte and hematopoietic stem-cell engraftment","volume":"76","author":"Shultz","year":"2003","journal-title":"Transplantation"},{"key":"B19","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1146\/annurev-pathol-052016-100332","article-title":"Humanized mouse models of clinical disease","volume":"12","author":"Walsh","year":"2017","journal-title":"Annu Rev Pathol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2009.103","article-title":"Unique features of NK cell development during ontogeny revealed in studies of RAG-1-deficient mice","volume":"88","author":"Chambers","year":"2010","journal-title":"Immunol Cell Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2009.94","article-title":"A potential role for RAG-1 in NK cell development revealed by analysis of NK cells during ontogeny","volume":"88","author":"Andrews","year":"2010","journal-title":"Immunol Cell Biol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1538\/expanim1978.29.1_1","article-title":"Breeding of a non-obese, diabetic strain of mice","volume":"29","author":"Makino","year":"1980","journal-title":"Jikken dobutsu. Exp Anim"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/172.4.974","article-title":"High levels of human peripheral blood mononuclear cell engraftment and enhanced susceptibility to human immunodeficiency virus type 1 infection in NOD\/LtSz-scid\/scid mice","volume":"172","author":"Hesselton","year":"1995","journal-title":"J Infect Dis"},{"key":"B24","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.jim.2014.06.009","article-title":"The use of BLT humanized mice to investigate the immune reconstitution of the gastrointestinal tract","volume":"410","author":"Wahl","year":"2014","journal-title":"J Immunol Methods"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.88533","article-title":"Chemoattractant-mediated leukocyte trafficking enables HIV dissemination from the genital mucosa","volume":"2","author":"Deruaz","year":"2017","journal-title":"JCI Insight"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.78.24.13891-13900.2004","article-title":"Experimental infection of NOD\/SCID mice reconstituted with human CD34+ cells with Epstein-Barr virus","volume":"78","author":"Islas-Ohlmayer","year":"2004","journal-title":"J Virol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5402.682","article-title":"Transduction of human CD34+ cells that mediate long-term engraftment of NOD\/SCID mice by HIV vectors","volume":"283","author":"Miyoshi","year":"1999","journal-title":"Sci (New York N.Y.)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.02017","article-title":"Enhanced antibody responses in a novel NOG transgenic mouse with restored lymph node organogenesis","volume":"8","author":"Takahashi","year":"2017","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2001-12-0207","article-title":"NOD\/SCID\/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells","volume":"100","author":"Ito","year":"2002","journal-title":"Blood"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.10.6477","article-title":"Human lymphoid and myeloid cell development in NOD\/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells","volume":"174","author":"Shultz","year":"2005","journal-title":"J Immunol (Baltimore Md. 1950)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03753.x","article-title":"Non-obese diabetic-recombination activating gene-1 (NOD-Rag1 null) interleukin (IL)-2 receptor common gamma chain (IL2r gamma null) null mice: a radioresistant model for human lymphohaematopoietic engraftment","volume":"154","author":"Pearson","year":"2008","journal-title":"Clin Exp Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/86531","article-title":"Generation of HIV latency during thymopoiesis","volume":"7","author":"Brooks","year":"2001","journal-title":"Nat Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.clim.2009.12.008","article-title":"Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation","volume":"135","author":"Brehm","year":"2010","journal-title":"Clin Immunol (Orlando Fla.)"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2131\/jts.34.123","article-title":"Higher susceptibility of NOG mice to xenotransplanted tumors","volume":"34","author":"Machida","year":"2009","journal-title":"J toxicol Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2009.03933.x","article-title":"Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complex","volume":"157","author":"King","year":"2009","journal-title":"Clin Exp Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.158","article-title":"AML xenograft efficiency is significantly improved in NOD\/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3","volume":"24","author":"Wunderlich","year":"2010","journal-title":"Leukemia"},{"key":"B37","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s11427-010-0059-7","article-title":"Current humanized mouse models for studying human immunology and HIV-1 immuno-pathogenesis","volume":"53","author":"Zhang","year":"2010","journal-title":"Sci China. Life Sci"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103660","article-title":"Development of mature and functional human myeloid subsets in hematopoietic stem cell-engrafted NOD\/SCID\/IL2r\u03b3KO mice","volume":"188","author":"Tanaka","year":"2012","journal-title":"J Immunol (Baltimore Md. 1950)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0014-5793(02)02703-5","article-title":"SHPS-1, a multifunctional transmembrane glycoprotein","volume":"519","author":"Oshima","year":"2002","journal-title":"FEBS Lett"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/nri1859","article-title":"The SIRP family of receptors and immune regulation","volume":"6","author":"Barclay","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.tcb.2008.12.001","article-title":"Functions and molecular mechanisms of the CD47-SIRPalpha signalling pathway","volume":"19","author":"Matozaki","year":"2009","journal-title":"Trends Cell Biol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1083\/jcb.200708043","article-title":"Inhibition of \"self\" engulfment through deactivation of myosin-II at the phagocytic synapse between human cells","volume":"180","author":"Tsai","year":"2008","journal-title":"J Cell Biol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101398108","article-title":"Functional CD47\/signal regulatory protein alpha (SIRP(alpha)) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo","volume":"108","author":"Legrand","year":"2011","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/ni1527","article-title":"Polymorphism in sirpa modulates engraftment of human hematopoietic stem cells","volume":"8","author":"Takenaka","year":"2007","journal-title":"Nat Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-06-440354","article-title":"Polymorphic sirpa is the genetic determinant for NOD-based mouse lines to achieve efficient human cell engraftment","volume":"121","author":"Yamauchi","year":"2013","journal-title":"Blood"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0071-6","article-title":"A human immune system mouse model with robust lymph node development","volume":"15","author":"Li","year":"2018","journal-title":"Nat Methods"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/art.30424","article-title":"Engraftment of peripheral blood mononuclear cells from systemic lupus erythematosus and antiphospholipid syndrome patient donors into BALB-RAG-2-\/- IL-2R\u03b3-\/- mice: a promising model for studying human disease","volume":"63","author":"Andrade","year":"2011","journal-title":"Arthritis rheumatism"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.816956","article-title":"Humanized mouse models of systemic lupus erythematosus: Opportunities and challenges","volume":"12","author":"Chen","year":"2021","journal-title":"Front Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.AID-0003-2012","article-title":"Humanized mice for studying human immune responses and generating human monoclonal antibodies","volume":"2","author":"Akkina","year":"2014","journal-title":"Microbiol Spectr"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxp050","article-title":"The analysis of the functions of human b and T cells in humanized NOD\/shi-scid\/gammac(null) (NOG) mice (hu-HSC NOG mice)","volume":"21","author":"Watanabe","year":"2009","journal-title":"Int Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2010.04.012","article-title":"Role of thymic cortex-specific self-peptides in positive selection of T cells","volume":"22","author":"Takahama","year":"2010","journal-title":"Semin Immunol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.smim.2007.12.002","article-title":"Plasma cell development: from b-cell subsets to long-term survival niches","volume":"20","author":"Fairfax","year":"2008","journal-title":"Semin Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019826","article-title":"Expression of HLA class II molecules in humanized NOD.Rag1KO.IL2RgcKO mice is critical for development and function of human T and b cells","volume":"6","author":"Danner","year":"2011","journal-title":"PloS One"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.6.2635","article-title":"HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis","volume":"183","author":"Ito","year":"1996","journal-title":"J Exp Med"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.677970","article-title":"Transfer of PBMC from SSc patients induces autoantibodies and systemic inflammation in Rag2-\/-\/IL2rg-\/- mice","volume":"12","author":"Yue","year":"2021","journal-title":"Front Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01943","article-title":"Xenogeneic graft-Versus-Host disease in humanized NSG and NSG-HLA-A2\/HHD mice","volume":"9","author":"Ehx","year":"2018","journal-title":"Front Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2018.1518948","article-title":"Establishment of peripheral blood mononuclear cell-derived humanized lung cancer mouse models for studying efficacy of PD-L1\/PD-1 targeted immunotherapy","volume":"10","author":"Lin","year":"2018","journal-title":"mAbs"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.8.1.113","article-title":"Use of humanized severe combined immunodeficient mice for human vaccine development","volume":"8","author":"Koo","year":"2009","journal-title":"Expert Rev Vaccines"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181c90242","article-title":"NOD-scid IL2rgamma(null) mouse model of human skin transplantation and allograft rejection","volume":"89","author":"Racki","year":"2010","journal-title":"Transplantation"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.034","article-title":"T Cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice","volume":"134","author":"Kumar","year":"2008","journal-title":"Cell"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2017.07.029","article-title":"Modeling hepatitis virus infections and treatment strategies in humanized mice","volume":"25","author":"Kremsdorf","year":"2017","journal-title":"Curr Opin Virol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.734471","article-title":"Epstein Barr Virus: Development of vaccines and immune cell therapy for EBV-associated diseases","volume":"12","author":"Cui","year":"2021","journal-title":"Front Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02895","article-title":"Role of herpes simplex virus type 1 (HSV-1) glycoprotein K (gK) pathogenic CD8(+) T cells in exacerbation of eye disease","volume":"9","author":"Jaggi","year":"2018","journal-title":"Front Immunol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.coviro.2015.06.006","article-title":"Humanized mouse models of human cytomegalovirus infection","volume":"13","author":"Crawford","year":"2015","journal-title":"Curr Opin Virol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-7230-7_19","article-title":"Animal models of human gammaherpesvirus infections","volume":"1045","author":"Fujiwara","year":"2018","journal-title":"Adv Exp Med Biol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2007.06.007","article-title":"Factors affecting human T cell engraftment, trafficking, and associated xenogeneic graft-vs-host disease in NOD\/SCID beta2mnull mice","volume":"35","author":"Nervi","year":"2007","journal-title":"Exp Hematol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.07.001","article-title":"Humanized mice for the study of immuno-oncology","volume":"39","author":"De La Rochere","year":"2018","journal-title":"Trends Immunol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201800636R","article-title":"Lack of acute xenogeneic graft- versus-host disease, but retention of T-cell function following engraftment of human peripheral blood mononuclear cells in NSG mice deficient in MHC class I and II expression","volume":"33","author":"Brehm","year":"2019","journal-title":"FASEB J"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.04.022","article-title":"Humanized mice efficiently engrafted with fetal hepatoblasts and syngeneic immune cells develop human monocytes and NK cells","volume":"65","author":"Billerbeck","year":"2016","journal-title":"J Hepatol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11007","article-title":"Therapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist","volume":"7","author":"Cao","year":"2016","journal-title":"Nat Commun"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1172\/jci89364","article-title":"Versatile humanized niche model enables study of normal and malignant human hematopoiesis","volume":"127","author":"Abarrategi","year":"2017","journal-title":"J Clin Invest"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095921","article-title":"Human hemato-lymphoid system mice: current use and future potential for medicine","volume":"31","author":"Rongvaux","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-166-6_30","article-title":"Humanized mice for studying human leukocyte integrins in vivo","volume":"757","author":"Kim","year":"2012","journal-title":"Methods Mol Biol (Clifton N.J.)"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00340","article-title":"Immune activations and viral tissue compartmentalization during progressive HIV-1 infection of humanized mice","volume":"10","author":"Su","year":"2019","journal-title":"Front Immunol"},{"key":"B75","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1186\/s12967-015-0539-4","article-title":"Recovery of a human natural antibody against the noncollagenous-1 domain of type IV collagen using humanized models","volume":"13","author":"Worni-Schudel","year":"2015","journal-title":"J Trans Med"},{"key":"B76","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1016\/j.humimm.2009.06.005","article-title":"Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid\/gammac-\/-, balb\/c-Rag1-\/-gammac-\/- and C.B-17-scid\/bg immunodeficient mice","volume":"70","author":"Lepus","year":"2009","journal-title":"Hum Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-8-65","article-title":"The utility of the new generation of humanized mice to study HIV-1 infection: transmission, prevention, pathogenesis, and treatment","volume":"8","author":"Berges","year":"2011","journal-title":"Retrovirology"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2011.06310.x","article-title":"Humanized mice as a preclinical tool for infectious disease and biomedical research","volume":"1245","author":"Shultz","year":"2011","journal-title":"Ann New York Acad Sci"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1996.0024","article-title":"Development and applications of the SCID-hu mouse model","volume":"8","author":"McCune","year":"1996","journal-title":"Semin Immunol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1126\/science.241.4873.1632","article-title":"The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function","volume":"241","author":"McCune","year":"1988","journal-title":"Sci (New York N.Y.)"},{"key":"B81","first-page":"S5","article-title":"Murine models for HIV disease","volume":"13","author":"Jamieson","year":"1999","journal-title":"AIDS (London England)"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4388","article-title":"Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus\/liver and CD34+ cell transplantation","volume":"108","author":"Lan","year":"2006","journal-title":"Blood"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-75647-7_10","article-title":"Functional and phenotypic characterization of the humanized BLT mouse model","volume":"324","author":"Wege","year":"2008","journal-title":"Curr topics Microbiol Immunol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2011.05.013","article-title":"Superior human leukocyte reconstitution and susceptibility to vaginal HIV transmission in humanized NOD-scid IL-2R\u03b3(-\/-) (NSG) BLT mice","volume":"417","author":"Stoddart","year":"2011","journal-title":"Virology"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.02207-08","article-title":"Induction of robust cellular and humoral virus-specific adaptive immune responses in human immunodeficiency virus-infected humanized BLT mice","volume":"83","author":"Brainard","year":"2009","journal-title":"J Virol"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/qad.0000000000001674","article-title":"An advanced BLT-humanized mouse model for extended HIV-1 cure studies","volume":"32","author":"Lavender","year":"2018","journal-title":"AIDS (London England)"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2809-5_21","article-title":"Humanized mice to study human T cell development","volume":"1323","author":"Bonte","year":"2016","journal-title":"Methods Mol Biol (Clifton N.J.)"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-07911-0_11","article-title":"Humanized mice to study Fc\u03b3R function","volume":"382","author":"Bournazos","year":"2014","journal-title":"Curr topics Microbiol Immunol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2013.05.012","article-title":"Humanized mice for the study of infectious diseases","volume":"25","author":"Brehm","year":"2013","journal-title":"Curr Opin Immunol"},{"key":"B90","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.chom.2018.12.008","article-title":"HIV-1 balances the fitness costs and benefits of disrupting the host cell actin cytoskeleton early after mucosal transmission","volume":"25","author":"Usmani","year":"2019","journal-title":"Cell Host Microbe"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2016.0193","article-title":"Propagating humanized BLT mice for the study of human immunology and immunotherapy","volume":"25","author":"Smith","year":"2016","journal-title":"Stem Cells Dev"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3791\/4181","article-title":"Using the BLT humanized mouse as a stem cell based gene therapy tumor model","volume":"18","author":"Vatakis","year":"2012","journal-title":"J visualized experiments"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2000.01099.x","article-title":"Mouse strain and conditioning regimen determine survival and function of human leucocytes in immunodeficient mice","volume":"119","author":"Tournoy","year":"2000","journal-title":"Clin Exp Immunol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199512000-00020","article-title":"The SCID mouse reaction to human peripheral blood mononuclear leukocyte engraftment. neutrophil recruitment induced expression of a wide spectrum of murine cytokines and mouse leukopoiesis, including thymic differentiation","volume":"60","author":"Santini","year":"1995","journal-title":"Transplantation"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000583","article-title":"Long-term human CD34+ stem cell-engrafted nonobese diabetic\/SCID\/IL-2R gamma(null) mice show impaired CD8+ T cell maintenance and a functional arrest of immature NK cells","volume":"185","author":"Andr\u00e9","year":"2010","journal-title":"J Immunol (Baltimore Md. 1950)"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.2.481","article-title":"Human growth factor-enhanced regeneration of transplantable human hematopoietic stem cells in nonobese diabetic\/severe combined immunodeficient mice","volume":"93","author":"Cashman","year":"1999","journal-title":"Blood"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302391","article-title":"FLT3-ligand treatment of humanized mice results in the generation of large numbers of CD141+ and CD1c+ dendritic cells in vivo","volume":"192","author":"Ding","year":"2014","journal-title":"J Immunol (Baltimore Md. 1950)"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2010.04.008","article-title":"Characterization and IL-15 dependence of NK cells in humanized mice","volume":"216","author":"Pek","year":"2011","journal-title":"Immunobiology"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012009","article-title":"Lentiviral vector delivery of human interleukin-7 (hIL-7) to human immune system (HIS) mice expands T lymphocyte populations","volume":"5","author":"O'Connell","year":"2010","journal-title":"PloS One"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912274106","article-title":"Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice","volume":"106","author":"Chen","year":"2009","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2858","article-title":"Development and function of human innate immune cells in a humanized mouse model","volume":"32","author":"Rongvaux","year":"2014","journal-title":"Nat Biotechnol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-10-676452","article-title":"Peripheral blood CD34(+) cells efficiently engraft human cytokine knock-in mice","volume":"128","author":"Saito","year":"2016","journal-title":"Blood"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203543","article-title":"Establishment of a human allergy model using human IL-3\/GM-CSF-transgenic NOG mice","volume":"191","author":"Ito","year":"2013","journal-title":"J Immunol (Baltimore Md. 1950)"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019524108","article-title":"Human thrombopoietin knock-in mice efficiently support human hematopoiesis in vivo","volume":"108","author":"Rongvaux","year":"2011","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-301507","article-title":"Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor-, granulocyte-macrophage colony-stimulating factor-, and interleukin-3-expressing NOD-SCID IL2R\u03b3(null) humanized mice","volume":"117","author":"Billerbeck","year":"2011","journal-title":"Blood"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-456566","article-title":"Enhanced normal short-term human myelopoiesis in mice engineered to express human-specific myeloid growth factors","volume":"121","author":"Miller","year":"2013","journal-title":"Blood"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.1988.053.01.060","article-title":"Macrophage colony-stimulating factor, CSF-1, and its proto-oncogene-encoded receptor","volume":"53","author":"Sherr","year":"1988","journal-title":"Cold Spring Harbor Symp quantitative Biol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04802-1","article-title":"Inflammasome activation in infected macrophages drives COVID-19 pathology","volume":"606","author":"Sefik","year":"2022","journal-title":"Nature"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0609.2001.066004221.x","article-title":"Changes in murine bone marrow macrophages and erythroid burst-forming cells following the intravenous injection of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP)","volume":"66","author":"Giuliani","year":"2001","journal-title":"Eur J haematol"},{"key":"B110","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1146\/annurev-immunol-032713-120142","article-title":"The interaction between signal regulatory protein alpha (SIRP\u03b1) and CD47: structure, function, and therapeutic target","volume":"32","author":"Barclay","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-00461-z","article-title":"Considerations for diagnostic COVID-19 tests","volume":"19","author":"Vandenberg","year":"2021","journal-title":"Nat Rev Microbiol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101205","article-title":"Aging in COVID-19: Vulnerability, immunity and intervention","volume":"65","author":"Chen","year":"2021","journal-title":"Ageing Res Rev"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2020.112830","article-title":"Diagnosis of COVID-19 for controlling the pandemic: A review of the state-of-the-art","volume":"174","author":"Taleghani","year":"2021","journal-title":"Biosensors bioelectronics"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1007579\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T19:02:11Z","timestamp":1678302131000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1007579\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,19]]},"references-count":113,"alternative-id":["10.3389\/fimmu.2022.1007579"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1007579","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,19]]},"article-number":"1007579"}}