Development and Organization of the Secondary and Tertiary Lymphoid Organs: Influence of Microbial and Food Antigens

Author(s): Thea Magrone*, Emilio Jirillo.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 19 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Secondary lymphoid organs (SLO) are distributed in many districts of the body and, especially, lymph nodes, spleen and gut-associated lymphoid tissue are the main cellular sites. On the other hand, tertiary lymphoid organs (TLO) are formed in response to inflammatory, infectious, autoimmune and neoplastic events.

Developmental Studies: In the present review, emphasis will be placed on the developmental differences of SLO and TLO between small intestine and colon and on the role played by various chemokines and cell receptors. Undoubtedly, microbiota is indispensable for the formation of SLO and its absence leads to their poor formation, thus indicating its strict interaction with immune and non immune host cells. Furthermore, food antigens (for example, tryptophan derivatives, flavonoids and byphenils) bind the aryl hydrocarbon receptor on innate lymphoid cells (ILCs), thus promoting the development of postnatal lymphoid tissues. Also retinoic acid, a metabolite of vitamin A, contributes to SLO development during embryogenesis. Vitamin A deficiency seems to account for reduction of ILCs and scarce formation of solitary lymphoid tissue.

Translational Studies: The role of lymphoid organs with special reference to intestinal TLO in the course of experimental and human disease will also be discussed.

Future Perspectives: Finally, a new methodology, the so-called “gut-in-a dish”, which has facilitated the in vitro interaction study between microbe and intestinal immune cells, will be described.

Keywords: Innate lymphoid cells, microbiota, polyphenols, secondary lymphoid organs, tertiary lymphoid organs, vitamins.

[1]
Buettner, M.; Lochner, M. Development and function of secondary and tertiary lymphoid organs in the small intestine and the colon. Front. Immunol., 2016, 7, 342.
[2]
Cancro, M.P.; Kearney, J.F. B cell positive selection: Road map to the primary repertoire? J. Immunol., 2004, 173, 15-29.
[3]
Boehm, T.; Bleul, C.C. The evolutionary history of lymphoid organs. Nat. Immunol., 2007, 8, 131-135.
[4]
Brandtzaeg, P.; Kiyono, H.; Pabst, R.; Russell, M.W. Terminology: Nomenclature of mucosa-associated lymphoid tissue. Mucosal Immunol., 2008, 1, 31-37.
[5]
van de Pavert, S.A.; Mebius, R.E. New insights into the development of lymphoid tissues. Nat. Rev. Immunol., 2010, 10, 664-674.
[6]
Randall, T.D.; Mebius, R.E. The development and function of mucosal lymphoid tissues: A balancing act with micro-organisms. Mucosal Immunol., 2014, 7, 455-466.
[7]
Shen, Z.H.; Zhu, C.X.; Quan, Y.; Yang, Z.Y.; Wu, S.; Luo, W.W.; Tan, B.; Wang, X.Y. Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J. Gastroenterol., 2018, 24, 5-14.
[8]
Walker, W.A. Bacterial colonization of the newborn gut, immune development, and prevention of disease. isolauri e, sherman pm, walker wa (eds): Intestinal microbiome: Functional aspects in health and disease. Nestle Nutr. Inst. Workshop Ser., 2017, 88, 23– 33.
[9]
Jones, G.W.; Hill, D.G.; Jones, S.A. Understanding immune cells in tertiary lymphoid organ development: It is all starting to come together. Front. Immunol., 2016, 7, 401.
[10]
Vondenhoff, M.F.; Greuter, M.; Goverse, G.; Elewaut, D.; Dewint, P.; Ware, C.F.; Hoorweg, K.; Kraal, G.; Mebius, R.E. LTbetaR signaling induces cytokine expression and up-regulates lymphangiogenic factors in lymph node anlagen. J. Immunol., 2009, 182, 5439-5445.
[11]
Bajénoff, M.; Egen, J.G.; Koo, L.Y.; Laugier, J.P.; Brau, F.; Glaichenhaus, N.; Germain, R.N. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity, 2006, 25, 989-1001.
[12]
Jarjour, M.; Jorquera, A.; Mondor, I.; Wienert, S.; Narang, P.; Mark, C.C.; Klauschen, F.; Bajénoff, M. Fate mapping reveals origin and dynamics of lymph node follicular dendritic cells. J. Exp. Med., 2014, 211, 1109-1122.
[13]
Katakai, T. Marginal reticular cells: A stromal subset directly descended from the lymphoid tissue organizer. Front. Immunol., 2012, 3, 200.
[14]
Lügering, A.; Ross, M.; Sieker, M. Heidemann,J.; Williams, I.R.; Domschke, W.; Kucharzik, T. CCR6 identifies lymphoid tissue inducer cells within cryptopatches. Clin. Exp. Immunol., 2010, 160, 440-449.
[15]
Chappaz, S.; Gärtner, C.; Rodewald, H.R.; Finke, D. Kit ligand and Il7 differentially regulate Peyer’s patch and lymph node development. J. Immunol., 2010, 185, 3514-3519.
[16]
Adachi, S.; Yoshida, H.; Honda, K.; Maki, K.; Saijo, K.; Ikuta, K.; Saito, T.; Nishikawa, S.I. Essential role of IL-7 receptor alpha in the formation of Peyer’s patch anlage. Int. Immunol., 1998, 10, 1-6.
[17]
Nishikawa, S.; Honda, K.; Vieira, P.; Yoshida, H. Organogenesis of peripheral lymphoid organs. Immunol. Rev., 2003, 195, 72-80.
[18]
Rönnstrand, L. Signal transduction via the stem cell factor receptor/c-Kit. Cell. Mol. Life Sci., 2004, 61, 2535-2548.
[19]
Veiga-Fernandes, H.; Coles, M.C.; Foster, K.E.; Patel, A.; Williams, A.; Natarajan, D.; Barlow, A.; Pachnis, V.; Kioussis, D. Tyrosine kinase receptor RET is a key regulator of Peyer’s patch organogenesis. Nature, 2007, 446, 547-551.
[20]
Kanamori, Y.; Ishimaru, K.; Nanno, M.; Maki, K.; Ikuta, K.; Nariuchi, H.; Ishikawa, H. Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit+ IL-7R+ Thy1+ lympho-hemopoietic progenitors develop. J. Exp. Med., 1996, 184, 1449-1459.
[21]
Eberl, G.; Littman, D.R. Thymic origin of intestinal alphabeta T cells revealed by fate mapping of ROR gammat+ cells. Science, 2004, 305, 248-251.
[22]
Hamada, H.; Hiroi, T.; Nishiyama, Y.; Takahashi, H.; Masunaga, Y.; Hachimura, S.; Kaminogawa, S.; Takahashi-Iwanaga, H.; Iwanaga, T.; Kiyono, H.; Yamamoto, H.; Ishikawa, H. Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J. Immunol., 2002, 168, 57-64.
[23]
McDonald, K.G.; McDonough, J.S.; Dieckgraefe, B.K.; Newberry, R.D. Dendritic cells produce CXCL13 and participate in the development of murine small intestine lymphoid tissues. Am. J. Pathol., 2010, 176, 2367-2377.
[24]
Tsuji, M.; Suzuki, K.; Kitamura, H.; Maruya, M.; Kinoshita, K.; Ivanov, I.I.; Itoh, K.; Littman, D.R.; Fagarasan, S. Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity, 2008, 29, 261-271.
[25]
Velaga, S.; Herbrand, H.; Friedrichsen, M.; Jiong, T.; Dorsch, M.; Hoffmann, M.W.; Förster, R.; Pabst, O. Chemokine receptor CXCR5 supports solitary intestinal lymphoid tissue formation, B cell homing, and induction of intestinal IgA responses. J. Immunol., 2009, 182, 2610-2619.
[26]
Baptista, A.P.; Olivier, B.J.; Goverse, G.; Greuter, M.; Knippenberg, M.; Kusser, K.; Domingues, R.G.; Veiga-Fernandes, H.; Luster, A.D.; Lugering, A.; Randall, T.D.; Cupedo, T.; Mebius, R.E. Colonic patch and colonic SILT development are independent and differentially regulated events. Mucosal Immunol., 2013, 6, 511-521.
[27]
Cherrier, M.S.; Eberl, G. Notch, Id2, and RORγt sequentially orchestrate the fetal development of lymphoid tissue inducer cells. J. Exp. Med., 2012, 209, 729-740.
[28]
Lochner, M.; Ohnmacht, C.; Presley, L.; Bruhns, P.; Si-Tahar, M.; Sawa, S.; Eberl, G. Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORgammat+ and LTi cells. J. Exp. Med., 2011, 208, 125-134.
[29]
Sawa, S.; Cherrier, M.; Lochner, M.; Satoh-Takayama, N.; Fehling, H.J.; Langa, F.; Di Santo, J.P.; Eberl, G. Lineage relationship analysis of RORgammat+ innate lymphoid cells. Science, 2010, 330, 665-669.
[30]
Rangel-Moreno, J.; Carragher, D.M. de la Luz Garcia-Hernandez. M.; Hwang, J.Y.; Kusser, K.; Hartson, L.; Kolls, J.K.; Khader, S.A.; Randall, T.D. The development of inducible bronchus-associated lymphoid tissue depends on IL-17. Nat. Immunol., 2011, 12, 639-646.
[31]
Kweon, M.N.; Yamamoto, M.; Rennert, P.D.; Park, E.J.; Lee, A.Y.; Chang, S.Y.; Hiroi, T.; Nanno, M.; Kiyono, H. Prenatal blockage of lymphotoxin beta receptor and TNF receptor p55 signaling cascade resulted in the acceleration of tissue genesis for isolated lymphoid follicles in the large intestine. J. Immunol., 2005, 174, 4365-4372.
[32]
McNamee, E.N.; Masterson, J.C.; Jedlicka, P.; Collins, C.B.; Williams, I.R.; Rivera-Nieves, J. Ectopic lymphoid tissue alters the chemokine gradient, increases lymphocyte retention and exacerbates murine ileitis. Gut, 2013, 62, 53-62.
[33]
Fernandez-Salguero, P.M.; Ward, J.M.; Sundberg, J.P.; Gonzalez, F.J. Lesions of aryl-hydrocarbon receptor-deficient mice. Vet. Pathol., 1997, 34, 605-614.
[34]
Olivier, B.J.; Cailotto, C.; van der Vliet, J.; Knippenberg, M.; Greuter, M.J.; Hilbers, F.W.; Konijn, T.; Te Velde, A.A.; Nolte, M.A.; Boeckxstaens, G.E.; de Jonge, W.J.; Mebius, R.E. Vagal innervation is required for the formation of tertiary lymphoid tissue in colitis. Eur. J. Immunol., 2016, 46, 2467-2480.
[35]
Gaboriau-Routhiau, V.; Rakotobe, S.; Lécuyer, E.; Mulder, I.; Lan, A.; Bridonneau, C.; Rochet, V.; Pisi, A.; De Paepe, M.; Brandi, G.; Eberl, G.; Snel, J.; Kelly, D.; Cerf-Bensussan, N. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity, 2009, 31, 677-689.
[36]
Ivanov, I.I.; Atarashi, K.; Manel, N.; Brodie, E.L.; Shima, T.; Karaoz, U.; Wei, D.; Goldfarb, K.C.; Santee, C.A.; Lynch, S.V.; Tanoue, T.; Imaoka, A.; Itoh, K.; Takeda, K.; Umesaki, Y.; Honda, K.; Littman, D.R. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell, 2009, 139, 485-498.
[37]
Lécuyer, E.; Rakotobe, S.; Lengliné-Garnier, H.; Lebreton, C.; Picard, M.; Juste, C.; Fritzen, R.; Eberl, G.; McCoy, K.D.; Macpherson, A.J.; Reynaud, C.A.; Cerf-Bensussan, N.; Gaboriau-Routhiau, V. Segmented filamentous bacterium uses secondary and tertiary lymphoid tissues to induce gut IgA and specific T helper 17 cell responses. Immunity, 2014, 40, 608-620.
[38]
Shiu, J.; Piazuelo, M.B.; Ding, H.; Czinn, S.J.; Drakes, M.L.; Banerjee, A.; Basappa, N.; Kobayashi, K.S.; Fricke, W.F.; Blanchard, T.G. Gastric LTi cells promote lymphoid follicle formation but are limited by IRAK-M and do not alter microbial growth. Mucosal Immunol., 2015, 8, 1047-1059.
[39]
Little, M.C.; Bell, L.V.; Cliffe, L.J.; Else, K.J. The characterization of intraepithelial lymphocytes, lamina propria leukocytes, and isolated lymphoid follicles in the large intestine of mice infected with the intestinal nematode parasite Trichuris muris. J. Immunol., 2005, 175, 6713-6722.
[40]
Mundy, R.; MacDonald, T.T.; Dougan, G.; Frankel, G.; Wiles, S. Citrobacter rodentium of mice and man. Cell. Microbiol., 2005, 7, 1697-1706.
[41]
Tumanov, A.V.; Koroleva, E.P.; Guo, X.; Wang, Y.; Kruglov, A.; Nedospasov, S.; Fu, Y.X. Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge. Cell Host Microbe, 2011, 10, 44-53.
[42]
Barone, F.; Nayar, S.; Campos, J.; Cloake, T.; Withers, D.R.; Toellner, K.M.; Zhang, Y.; Fouser, L.; Fisher, B.; Bowman, S.; Rangel-Moreno, J.; Garcia-Hernandez Mde, L.; Randall, T.D.; Lucchesi, D.; Bombardieri, M.; Pitzalis, C.; Luther, S.A.; Buckley, C.D. IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs. Proc. Natl. Acad. Sci. USA, 2015, 112, 11024-11029.
[43]
Collado, M.C.; Rautava, S.; Aakko, J.; Isolauri, E.; Salminen, S. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci. Rep., 2016, 6, 23129.
[44]
Romano-Keeler, J.; Weitkamp, J.H. Maternal influences on fetal microbial colonization and immune development. Pediatr. Res., 2015, 77, 189-195.
[45]
Messer, J.S.; Liechty, E.R.; Vogel, O.A.; Chang, E.B. Evolutionary and ecological forces that shape the bacterial communities of the human gut. Mucosal Immunol., 2017, 10, 567-579.
[46]
Magrone, T.; Jirillo, E. The interaction between gut microbiota and age-related changes in immune function and inflammation. Immun. Ageing, 2013, 10, 31.
[47]
Calder, P.C.; Bosco, N.; Bourdet-Sicard, R.; Capuron, L.; Delzenne, N.; Doré, J.; Franceschi, C.; Lehtinen, M.J.; Recker, T.; Salvioli, S.; Visioli, F. Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition. Ageing Res. Rev., 2017, 40, 95-119.
[48]
Ríos-Covián, D.; Ruas-Madiedo, P.; Margolles, A.; Gueimonde, M.; de Los Reyes-Gavilán, C.G.; Salazar, N. Intestinal short chain fatty acids and their link with diet and human health. Front. Microbiol., 2016, 7, 185.
[49]
Magrone, T.; Jirillo, E. The interplay between the gut immune system and microbiota in health and disease: Nutraceutical intervention for restoring intestinal homeostasis. Curr. Pharm. Des., 2013, 19, 1329-1342.
[50]
Mazmanian, S.K.; Round, J.L.; Kasper, D.L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature, 2008, 453, 620-625.
[51]
Macpherson, A.J.; Geuking, M.B.; Slack, E.; Hapfelmeier, S.; McCoy, K.D. The habitat, double life, citizenship, and forgetfulness of IgA. Immunol. Rev., 2012, 245, 132-146.
[52]
Macpherson, A.J.; Yilmaz, B.; Limenitakis, J.P.; Ganal-Vonarburg, S.C. IgA function in relation to the intestinal microbiota. Annu. Rev. Immunol., 2018, 36, 359-381.
[53]
Donaldson, D.S.; Bradford, B.M.; Artis, D.; Mabbott, N.A. Reciprocal regulation of lymphoid tissue development in the large intestine by IL-25 and IL-23. Mucosal Immunol., 2015, 8, 582-595.
[54]
Bouskra, D.; Brézillon, C.; Bérard, M.; Werts, C.; Varona, R.; Boneca, I.G.; Eberl, G. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature, 2008, 456, 507-510.
[55]
Zaph, C.; Du, Y.; Saenz, S.A.; Nair, M.G.; Perrigoue, J.G.; Taylor, B.C.; Troy, A.E.; Kobuley, D.E.; Kastelein, R.A.; Cua, D.J.; Yu, Y.; Artis, D. Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine. J. Exp. Med., 2008, 205, 2191-2198.
[56]
Sawa, S.; Lochner, M.; Satoh-Takayama, N.; Dulauroy, S.; Bérard, M.; Kleinschek, M.; Cua, D.; Di Santo, J.P.; Eberl, G. RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat. Immunol., 2011, 12, 320-326.
[57]
Esser, C.; Rannug, A. The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology. Pharmacol. Rev., 2015, 67, 259-279.
[58]
Kiss, E.A.; Vonarbourg, C.; Kopfmann, S.; Hobeika, E.; Finke, D.; Esser, C.; Diefenbach, A. Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science, 2011, 334, 1561-1565.
[59]
Lee, J.S.; Cella, M.; McDonald, K.G.; Garlanda, C.; Kennedy, G.D.; Nukaya, M.; Mantovani, A.; Kopan, R.; Bradfield, C.A.; Newberry, R.D.; Colonna, M. AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch. Nat. Immunol., 2011, 13, 144-151.
[60]
van de Pavert, S.A.; Mebius, R.E. New insights into the development of lymphoid tissues. Nat. Rev. Immunol., 2010, 10, 664-674.
[61]
Buckley, C.D.; Barone, F.; Nayar, S.; Bénézech, C.; Caamaño, J. Stromal cells in chronic inflammation and tertiary lymphoid organ formation. Annu. Rev. Immunol., 2015, 33, 715-745.
[62]
Sugiyama, M.; Nakato, G.; Jinnohara, T.; Akiba, H.; Okumura, K.; Ohno, H.; Yoshida, H. Expression pattern changes and function of RANKL during mouse lymph node microarchitecture development. Int. Immunol., 2012, 24, 369-378.
[63]
Chappaz, S.; Gärtner, C.; Rodewald, H.R.; Finke, D. Kit ligand and Il7 differentially regulate Peyer’s patch and lymph node development. J. Immunol., 2010, 185, 3514-3519.
[64]
Goverse, G.; Labao-Almeida, C.; Ferreira, M.; Molenaar, R.; Wahlen, S.; Konijn, T.; Koning, J.; Veiga-Fernandes, H.; Mebius, R.E. Vitamin a controls the presence of rorγ+ innate lymphoid cells and lymphoid tissue in the small intestine. J. Immunol., 2016, 196, 5148-5155.
[65]
Colbeck, E.J.; Ager, A.; Gallimore, A.; Jones, G.W. Tertiary lymphoid structures in cancer: drivers of antitumor immunity, immunosuppression, or bystander sentinels in disease? Front. Immunol., 2017, 8, 1830.
[66]
Sautès-Fridman, C.; Fridman, W.H. TLS in tumors: what lies within. Trends Immunol., 2016, 37, 1-2.
[67]
Joshi, N.S.; Akama-Garren, E.H.; Lu, Y.; Lee, D.Y.; Chang, G.P.; Li, A.; DuPage, M.; Tammela, T.; Kerper, N.R.; Farago, A.F.; Robbins, R.; Crowley, D.M.; Bronson, R.T.; Jacks, T. Regulatory t cells in tumor-associated tertiary lymphoid structures suppress anti-tumor t cell responses. Immunity, 2015, 43, 579-590.
[68]
Gobert, M.; Treilleux, I.; Bendriss-Vermare, N.; Bachelot, T.; Goddard-Leon, S.; Arfi, V.; Biota, C.; Doffin, A.C.; Durand, I.; Olive, D.; Perez, S.; Pasqual, N.; Faure, C. Ray-Coquard. I.; Puisieux, A.; Caux, C.; Blay, J.Y.; Ménétrier-Caux, C. Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. Cancer Res., 2009, 69, 2000-2009.
[69]
Finkin, S.; Yuan, D.; Stein, I.; Taniguchi, K.; Weber, A.; Unger, K.; Browning, J.L.; Goossens, N.; Nakagawa, S.; Gunasekaran, G.; Schwartz, M.E.; Kobayashi, M.; Kumada, H.; Berger, M.; Pappo, O.; Rajewsky, K.; Hoshida, Y.; Karin, M.; Heikenwalder, M.; Ben-Neriah, Y.; Pikarsky, E. Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nat. Immunol., 2015, 16, 1235-1244.
[70]
Coppola, D.; Nebozhyn, M.; Khalil, F.; Dai, H.; Yeatman, T.; Loboda, A.; Mulé, J.J. Unique ectopic lymph node-like structures present in human primary colorectal carcinoma are identified by immune gene array profiling. Am. J. Pathol., 2011, 179, 37-45.
[71]
Kim, M.H.; Taparowsky, E.J.; Kim, C.H. Retinoic acid differentially regulates the migration of innate lymphoid cell subsets to the gut. Immunity, 2015, 43, 107-119.
[72]
Croia, C.; Serafini, B.; Bombardieri, M.; Kelly, S.; Humby, F.; Severa, M.; Rizzo, F.; Coccia, E.M.; Migliorini, P.; Aloisi, F.; Pitzalis, C. Epstein-Barr virus persistence and infection of autoreactive plasma cells in synovial lymphoid structures in rheumatoid arthritis. Ann. Rheum. Dis., 2013, 72, 1559-1568.
[73]
Grewal, J.S.; Pilgrim, M.J.; Grewal, S.; Kasman, L.; Werner, P.; Bruorton, M.E.; London, S.D.; London, L. Salivary glands act as mucosal inductive sites via the formation of ectopic germinal centers after site-restricted MCMV infection. FASEB J., 2011, 25, 1680-1696.
[74]
Kobayashi, Y.; Watanabe, T. Synthesis of artificial lymphoid tissue with immunological function. Trends Immunol., 2010, 31, 422-428.
[75]
Suematsu, S.; Watanabe, T. Generation of a synthetic lymphoid tissue-like organoid in mice. Nat. Biotechnol., 2004, 22, 1539-1545.
[76]
Pan, W.R.; Suami, H.; Taylor, G.I. Senile changes in human lymph nodes. Lymphat. Res. Biol., 2008, 6, 77-83.
[77]
Ito, M.; Hiramatsu, H.; Kobayashi, K.; Suzue, K.; Kawahata, M.; Hioki, K.; Ueyama, Y.; Koyanagi, Y.; Sugamura, K.; Tsuji, K.; Heike, T.; Nakahata, T. NOD/SCID/gamma(c)(null) mouse: An excellent recipient mouse model for engraftment of human cells. Blood, 2002, 100, 3175-3182.
[78]
Shultz, L.D.; Lyons, B.L.; Burzenski, L.M.; Gott, B.; Chen, X.; Chaleff, S.; Kotb, M.; Gillies, S.D.; King, M.; Mangada, J.; Greiner, D.L.; Handgretinger, R. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J. Immunol., 2005, 174, 6477-6489.
[79]
Ishikawa, F.; Yasukawa, M.; Lyons, B.; Yoshida, S.; Miyamoto, T.; Yoshimoto, G.; Watanabe, T.; Akashi, K.; Shultz, L.D.; Harada, M. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor gamma chain(null) mice. Blood, 2005, 106, 1565-1573.
[80]
Saito, Y.; Uchida, N.; Tanaka, S.; Suzuki, N.; Tomizawa-Murasawa, M.; Sone, A.; Najima, Y.; Takagi, S.; Aoki, Y.; Wake, A.; Taniguchi, S.; Shultz, L.D.; Ishikawa, F. Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML. Nat. Biotechnol., 2010, 28, 275-280.
[81]
Zhang, L.; Kovalev, G.I.; Su, L. HIV-1 infection and pathogenesis in a novel humanized mouse model. Blood, 2007, 109, 2978-2981.
[82]
Legrand, N.; Ploss, A.; Balling, R.; Becker, P.D.; Borsotti, C.; Brezillon, N.; Debarry, J.; de Jong, Y.; Deng, H.; Di Santo, J.P.; Eisenbarth, S.; Eynon, E.; Flavell, R.A.; Guzman, C.A.; Huntington, N.D.; Kremsdorf, D.; Manns, M.P.; Manz, M.G.; Mention, J.J.; Ott, M.; Rathinam, C.; Rice, C.M.; Rongvaux, A.; Stevens, S.; Spits, H.; Strick-Marchand, H.; Takizawa, H.; van Lent, A.U.; Wang, C.; Weijer, K.; Willinger, T.; Ziegler, P. Humanized mice for modeling human infectious disease: Challenges, progress, and outlook. Cell Host Microbe, 2009, 6, 5-9.
[83]
Kurilshikov, A.; Wijmenga, C.; Fu, J.; Zhernakova, A. Host genetics and gut microbiome: challenges and perspectives. Trends Immunol., 2017, 38, 633-647.
[84]
Ivanov, I.I. Mucosal bioengineering: Gut in a dish. Trends Immunol., 2017, 38, 537-539.
[85]
Yissachar, N.; Zhou, Y.; Ung, L.; Lai, N.Y.; Mohan, J.F.; Ehrlicher, A.; Weitz, D.A.; Kasper, D.L.; Chiu, I.M.; Mathis, D.; Benoist, C. An intestinal organ culture system uncovers a role for the nervous system in microbe-immune crosstalk. Cell, 2017, 168, 1135-1148.
[86]
Atarashi, K.; Tanoue, T.; Ando, M.; Kamada, N.; Nagano, Y.; Narushima, S.; Suda, W.; Imaoka, A.; Setoyama, H.; Nagamori, T.; Ishikawa, E.; Shima, T.; Hara, T.; Kado, S.; Jinnohara, T.; Ohno, H.; Kondo, T.; Toyooka, K.; Watanabe, E.; Yokoyama, S.; Tokoro, S.; Mori, H.; Noguchi, Y.; Morita, H.; Ivanov, I.I.; Sugiyama, T.; Nuñez, G.; Camp, J.G.; Hattori, M.; Umesaki, Y.; Honda, K. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell, 2015, 163, 367-380.
[87]
Sefik, E.; Geva-Zatorsky, N.; Oh, S.; Konnikova, L.; Zemmour, D.; McGuire, A.M.; Burzyn, D.; Ortiz-Lopez, A.; Lobera, M.; Yang, J.; Ghosh, S.; Earl, A.; Snapper, S.B.; Jupp, R.; Kasper, D.; Mathis, D.; Benoist, C. Mucosal immunology. Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells. Science, 2015, 349, 993-997.
[88]
Ohnmacht, C.; Park, J.H.; Cording, S.; Wing, J.B.; Atarashi, K.; Obata, Y.; Gaboriau-Routhiau, V.; Marques, R.; Dulauroy, S.; Fedoseeva, M.; Busslinger, M.; Cerf-Bensussan, N.; Boneca, I.G.; Voehringer, D.; Hase, K.; Honda, K.; Sakaguchi, S.; Eberl, G. Mucosal immunology. The microbiota regulates type 2 immunity through RORγt+ T cells. Science, 2015, 349, 989-993.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 2
Year: 2019
Page: [128 - 135]
Pages: 8
DOI: 10.2174/1871530319666181128160411
Price: $58

Article Metrics

PDF: 24
HTML: 1