MorphologyMorphologyМорфология1026-35432949-2556Eco-Vector39873410.17816/morph.398734ArticlesСтатьиReview ArticlePANETH CELLS: HISTORY OF DISCOVERY, STRUCTURAL AND FUNCTIONAL CHARACTERISTICS AND THE ROLE IN THE MAINTENANCE OF HOMEOSTASIS IN THE SMALL INTESTINEКЛЕТКИ ПАНЕТА: ИСТОРИЯ ОТКРЫТИЯ, СТРУКТУРНО-ФУНКЦИОНАЛЬНЫЕ ХАРАКТЕРИСТИКИ И РОЛЬ В ПОДДЕРЖАНИИ ГОМЕОСТАЗА В ТОНКОЙ КИШКЕBykovV. L.БыковВладимир Лазаревич

кафедра гистологии, цитологии и эмбриологии

vbykov@spmu.rssi.ruFirst St. Petersburg I. P. Pavlov State Medical UniversityПервый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова150220141451VOL 145, NO1 (2014)ТОМ 145, №1 (2014)678009052023Copyright ©; 2014, Eco-VectorCopyright ©; 2014, Эко-Вектор2014Eco-VectorЭко-Векторhttps://j-morphology.com/1026-3543/article/view/398734

Cells with acidophilic granules in the crypts of the small intestine were first described, along with the other cells of intestinal epithelium, in 1872 by a well-known German anatomist, histologist and anthropologist G. A. Schwalbe, however they were named after an Austrian histologist and physiologist J. Paneth, who has performed their detailed morphological analysis in 1888. For many decades the role of Paneth cells (PCs) remained completely unclear, until in 1960–1970 the production of antimicrobial molecules by these cells was found. At present, it is established that PCs produce a broad spectrum of antimicrobial compounds, thus controlling the number and content of intestinal microbial populations. PCs are an important part of innate immunity defense mechanisms, however, by interacting with the other cells, they participate in the reactions of the adaptive immunity. By creating high concentrations of antimicrobial substances within the crypt, PCs protect intestinal stem cells from the damage by potentially pathogenic microorganisms, while by releasing some signaling molecules, they control the vital functions of these cells, being an important component of their niche. Affecting the host tissues and influencing the microbial populations, PCs play a significant role in the maintenance of homeostasis in the intestine.

Клетки с ацидофильными гранулами в криптах тонкой кишки были впервые описаны, наряду с другими клетками эпителия кишки, в 1872 г. известным немецким анатомом, гистологом и антропологом Г. А. Швальбе, однако они были названы именем австрийского гистолога и физиолога Й. Панета, который провел их подробный морфологический анализ в 1888 г. В течение многих десятилетий роль клеток Панета (КП) оставалась полностью неизвестной, пока в 1960–1970-е годы не была обнаружена выработка ими антимикробных молекул. В настоящее время установлено, что КП продуцируют широкий спектр антимикробных соединений, регулируя численность и качественный состав микробных популяций в кишке. КП является важной частью защитных механизмов врожденного иммунитета слизистой оболочки кишки, однако, взаимодействуя с другими клетками, они участвуют и в адаптивных иммунных реакциях. Создавая в крипте высокие концентрации антимикробных веществ, КП защищают кишечные стволовые клетки от повреждения потенциально патогенными микроорганизмами, а выделяя ряд сигнальных молекул, они регулируют жизнедеятельность этих клеток, входя в качестве важного компонента в состав их ниши. Воздействуя на ткани хозяина и влияя на микробные популяции, КП играют существенную роль в поддержании гомеостаза в кишке.

Paneth cellsintestineepitheliumdefense mechanismsклетки Панетакишкаэпителийзащитные механизмыЕлецкий Ю. К., Куликова О. В. и Цибулевский А. Ю. Реакция клеток Панета тощей кишки крыс на выключение блуждающих нервов (ультраструктурный анализ). Арх. анат., 1984, т. 86, вып. 4, с. 73–79.Ещенко В. А. Повреждение клеток Панета у крыс при введении дитизона и 8-аренсульфониламино холинов. Бюл. экспер. биол., 1977, т. 83, № 4, с. 494–496.Международные термины по цитологии и гистологии человека с официальным списком русских эквивалентов. Под ред. В. В. Банина и В. Л. Быкова. М., ГЭОТАР-Медиа, 2009, с. 84.Новицкий В. В., Ещенко Ю. В., Бовт В. Д. и др. Содержание цинка в клетках Панета и предстательной железы при действии хелатирующих и стрессовых факторов. Бюл. экспер. биол., 2011, т. 152, № 8, с. 140–143.Шахламов В. А. и Солнышкова Т. Г. Ультраструктурный и морфологический анализ реакции клеток Панета на введение холерного токсина. Бюл. экспер. биол., 1992, т. 63, № 4, с. 415–417.Ahonen A. Histochemical and electron microscopic observations on the development, neural control and function of the Paneth cells of the mouse. Acta Physiol. Scand., 1973, Suppl. 398, p. 1–71.Ahonen A. Long term effect of chemical sympathectomy on the small intestinal morphology of the mouse. J. Ultrastruct. Res., 1975, v. 50, p. 379–380.Ahonen A. and Penttilä A. Effect of glucagon and insulin on the Paneth cells of the mouse duodenum. Experientia, 1975, v. 31, p. 1074–1075.Andreu P., Colnot S., Godard C. et al. Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine. Development, 2005, v. 132, p. 1443–1451.Andreu P., Peignon G., Slomianny C. et al. A genetic study of the role of the Wnt/beta-catenin signalling in Paneth cell differentiation, Dev. Biol., 2008, v. 324, p. 288–296.Ayabe T., Ashida T., Kohgo Y. and Kono T. The role of Paneth cells and their antimicrobial peptides in innate host defense. Trends Microbiol., 2004, v. 12, №8, p. 394–398.Ayabe T., Satchell D. P., Pesendorfer P. et al. Activation of Paneth cell alpha-defensins in mouse small intestine. J. Biol. Chem., 2002, v. 277, p. 5219–5228.Ayabe T., Satchell D. P., Wilson C. L. et al. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat. Immunol., 2000, v. 1, №2, p. 113–118.Ayabe T., Wulff H., Darmoul D. et al. Modulation of mouse Paneth cell alpha-defensin secretion by mIKCa1, a Са2+activated, intermediate conductance potassium channel. J. Biol. Chem., 2002, v. 277, p. 3793–3800.Barker N., van Es J. H., Kuipers J. et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature, 2007, v. 449, p. 1003–1007.Barkla D. H. and Tutton P. J.M. Experimentally induced accumulation and depletion of Paneth cell granules J. Anat., 1974, v. 118, p. 389 (Abstract).Bastide P., Darido C., Pannequin J. et al. Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium. J. Cell Biol., 2007, v. 178, p. 635–648.Batlle E., Henderson J. T., Beghtel H. et al. β-Catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/EphrinB. Cell, 2002, v. 111, p. 251–263.Beal R. K., Powers C., Davison T. F. and Smith A. L. Immunological development of the avian gut. In: Avian Gut Function in Health and Disease. Ed. Perry G. C. Poultry Science Symposium Series, v. 28, Wallingford, CABI Publ., 2006, p. 85–104.Behnke O. and Moe H. An electron microscope study of mature and differentiating Paneth cells in the rat, especially of their endoplasmic reticulum and lysosomes. J. Cell Biol., 1964, v. 22, p. 633–652.Bevins C. L. and Salzman N. H. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat. Rev. Microbiol., 2011, v. 9, p. 356–368.Bizzozero G. Ueber die schlauchförmigen Drüsen des Magendarmkanals und die Beziehungen ihres Epithels zu dem Oberflachenepithel der Schleimhaut. Arch. mikrosk. Anat., 1889, Bd. 33, S. 216–246.Bjerknes M. and Cheng H. The stem cell zone of the small intestinal epithelium. I. Evidence from Paneth cells in the adult mouse. Am. J. Anat., 1981, v. 160, p. 51–63.Böhm A. A. und Davidoff M. von. Lehrbuch der Histologie des Menschen: einschliesslich der mikroskopischen Technik. Wiesbaden, J. F. Bergmann, 1895.Brandl K., Plitas G., Schnabl B. et al. MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection. J. Exp. Med., 2007, v. 204, p. 1891–1900.Bry L., Falk P., Huttner K. et al. Paneth cell differentiation in the developing intestine of normal and transgenic mice. Proc. Natl. Acad. Sci. USA, 1994, v. 91, p. 10335–10339.Cairnie A. B. Renewal of goblet and Paneth cells in the small intestine. Cell Tiss. Kinet., 1970, v. 3, p. 35–45.Cash H. L., Whitham C. V., Behrendt C. L. and Hooper L. V. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science, 2006, v. 313, p. 1126–1130.Cheng H. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. IV. Paneth cells. Am. J. Anat., 1974, v. 141, p. 521–536.Cheng H. and Leblond C. P. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types, Am. J. Anat., 1974, v. 141, p. 537–561.Cheng H., Merzel J. and Leblond C. P. Renewal of Paneth cells in the small intestine of the mouse. Am. J. Anat., 1969, v. 126, p. 507–525.Coutinho H. B., da Mota H. C., Coutinho V. B. et al. Absence of lysozyme (muramidase) in the intestinal Paneth cells of newborn infants with necrotising enterocolitis. J. Clin. Pathol., 1998, v. 51, №7, p. 512–514.Cunliffe R. N., Rose F. R., Keyte J. et al. Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease. Gut, 2001, v. 48, №2, p. 176–185.Deheragoda M. and Wright N. An update on the pathophysiology of the intestinal crypt. Curr. Diagn. Pathol., 2006, v. 12, p. 268–278.Dehkordi R. A.F. and Parchami A. Paneth cells distribution of small intestine in male rabbit: a light and electron microscopic study. World Appl. Sci. J., 2011, v. 14, №3, p. 485–489.Deschner E. E. Observations on the Paneth cell in human ileum. Exp. Cell Res., 1967, v. 47, p. 624–628.Dinsdale D. Ultrastructural localization of zinc and calcium within the granules of rat Paneth cells. J. Histochem. Cytochem., 1984, v. 32, p. 139–145.Di Sabatino A., Miceli E., Dhaliwal W. et al. Distribution, proliferation, and function of Paneth cells in uncomplicated and complicated adult celiac disease. Am. J. Clin. Pathol., 2008, v. 130, 1, p. 34–42.Dorland’s Illustrated Medical Dictionary. 32nd edit. Philadelphia, Saunders, 2012, p. 246.Ephick D. A. and Mahida Y.P. Paneth cells: their role in innate immunity and inflammatory disease. Gut, 2005, v. 54, №12, p. 1802–1809.Ergün E., Ergün L., Asti R. N. and Kürüm A. Light and electron microscopic morphology of Paneth cells in the sheep small intestine. Rev. Méd. Vét., 2003, v. 154, №5, p. 351–355.Erlandsen S. L., Parsons J. A. and Taylor T.D. Ultrastructural immunocytochemical localization of lysozyme in the Paneth cells of man. J. Histochem. Cytochem., 1974, v. 22, p. 401–413.Erlandsen S. L., Rodning C. B., Montero C. et al. Immunocytochemical identification and localization of immunoglobulin A within Paneth cells of the rat small intestine. J. Histochem. Cytochem., 1976, v. 24, p. 1085–1092.Farin H. F., van Es J. H. and Clevers H. Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells. Gastroenterology, 2012, v. 143, p. 1518–1529.Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat. Rev. Immunol., 2003, v. 3, p. 710–720.Garabedian E. M., Roberts L. J., McNevin M. S. and Gordon J. I. Examining the role of Paneth cells in the small intestine by lineage ablation in transgenic mice. J. Biol. Chem., 1997, v. 272, p. 23729–23740.Ghoos Y. and Vantrappen G. The cytochemical localization of lysozyme in Paneth cell granules. Histochem. J., 1971, v. 3, p. 175–178.Hall P.A., Coates P.I., Ansari B. and Hopwood D. Regulation of cell number in the mammalian gastrointestinal tract - the importance of apoptosis. J. Cell Sci., 1994, v. 107, p. 3569–3577.Hampton J. C. Effects of fixation on the morphology of Paneth cell granules. Stain Technol., 1965, v. 40, p. 283–291.Harwig S. S., Tan L., Qu X. D. et al. Bactericidal properties of murine intestinal phospholipase A2. J. Clin. Invest., 1995, v. 95, № 2, p. 603–610.Hertzog A. J. The Paneth cell. Am. J. Pathol., 1937, v. 13, p. 351–362.Hooper L. V., Stappenbeck T. S., Hong C. V. and Gordon J. I. Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat. Immunol., 2003, v. 4, p. 269–273.Ireland H., Houghton C., Howard L. and Winton D. J. Cellular inheritance of a Cre-activated reporter gene to determine Paneth cell longevity in the murine small intestine. Dev. Dyn., 2005, v. 233, p. 1332–1336.Ishizuya-Oka A. Regeneration of the amphibian intestinal epithelium under the control of stem cell niche. Develop. Growth Differ., 2007, v. 49, p. 99–107Ito T., Tanabe H., Ayabe T. et al. Paneth cells regulate both chemotaxis of immature dendritic cells and cytokine production from epithelial cells. Tohoku J. Exp. Med., 2012, v. 227, №1, p. 39–48.Kaufmann-Wolf M. Kurze Notiz über Belegzellen, Panethsche Zellen und basal gekörnte Zellen im Darm des Menschen. Anat. Anz., 1911, Bd. 39, S. 670–672.Keren D. F., Elliott H. L., Brown G. D. and Yardley J. H. Atrophy of villi with hypertrophy and hyperplasia of Paneth cells in isolated (thiry-vella) ileal loops in rabbits. Gastroenterology, 1975, v. 68, p. 83–93.Keshav S., Lawson L., Chung L. P. et al. Tumor necrosis factor mRNA localized to Paneth cells of normal murine intestinal epithelium by in situ hybridization. J. Exp. Med., 1990, v. 171, № 1, p. 327–332.Kim T.H., Escudero S. and Shivdasani R. A. Intact function of Lgr5 receptor expressing intestinal stem cells in the absence of Paneth cells. Proc. Natl. Acad. Sci. USA, 2012, v.109, p. 3932– 3937.Klockars M. and Osserman E. F. Localization of lysozyme in normal rat tissue by an immunoperoxidase method. J. Histochem. Cytochem., 1974, v. 22, p. 139–146.Lawrance I. C., Fiocchi C. and Chakravarti S. Ulcerative colitis and Crohn‘s disease: distinctive gene expression profiles and novel susceptibility candidate genes. Hum. Mol. Genet., 2001, v. 10, №5, p. 445–456.Leis O., Madrid J. F., Ballesta J. and Hernandez F. N- and O-linked oligosaccharides in the secretory granules of rat Paneth cells: an ultrastructural cytochemical study. J. Histochem. Cytochem., 1997, v. 45, p. 285–293Lendrum A. C. The phloxine-tartrazine method as general histological stain and for the demonstration of inclusion bodies. J. Pathol. Bacteriol., 1947, v. 59, p. 399–404.Lewin K. Histochemical observations on Paneth cells. J. Anat., 1969, v. 105, №1, p. 171–176.Lewin K. The Paneth cell in health and disease. Ann. Roy. Coll. Surg. Engl., 1969, v. 44, p. 23–37.Li L. and Clevers H. Coexistence of quiescent and active adult stem cells in mammals, Science, 2010, v. 327, p. 542–545.Lin P. W., Simon P. O., Gewirtz A. T. et al. Paneth cell cryptdins act in vitro as apical paracrine regulators of the innate inflammatory response. J. Biol. Chem., 2004, v. 279, p. 19902–19907.Lopez-Lewellyn J. and Erlandsen S. L. Cytodifferentiation of the rat Paneth cell: an immunocytochemical investigation in suckling and weanling animals. Am. J. Anat., 1980, v. 158, №3, p. 285–297.Mahida Y. R. Epithelial cell responses. Best Pract. Res. Clin. Gastroenterol., 2004, v. 18, №2, p. 241–253.Mallow E. B., Harris A., Salzman N. et al. Human enteric defensins. Gene structure and developmental expression. J. Biol. Chem., 1996, v. 271, p. 4038–4045.Mastroianni J. R. and Ouellette A. J. Alpha-defensins in enteric innate immunity: functional Paneth cell alpha-defensins in mouse colonic lumen. J. Biol. Chem., 2009, v. 284, №41, p. 27848–27856.Mathan M., Hughes J. and Whitehead R. The morphogenesis of the human Paneth cell. An immunocytochemical ultrastructural study. Histochemistry, 1987, v. 87, №1, p. 91–96.Möller P., Walczak H., Reidl S. et al. Paneth cells express high levels of CD95 ligand transcripts: a unique property among gastrointestinal epithelia. Am. J. Pathol., 1996, v. 149, №1, p. 9–13.Möller W. Anatomische Beiträge zur Frage von der Sekretion und Resorption in der Darmschleimhaut. Z. wissensch. Zool., 1899, Bd. 66, S. 69–135.Mori-Akiyama Y., van den Born M., van Es J. H. et al. SOX9 is required for the differentiation of Paneth cells in the intestinal epithelium. Gastroenterology, 2007, v. 133, p. 539–546.Nevalainen T. J., Laine V. J. and Grass D. S. Expression of human group II phospholipase A2 in transgenic mice. J. Histochem. Cytochem., 1997, v. 45, №8, p. 1109–1119.Ogawa K., Masutani K. and Shinonaga Y. Electron histochemical demonstration of acid phosphatase in the normal rat jejunum. J. Histochem. Cytochem., 1962, v. 10, p. 228–229.Ouellette A. J. Defensin-mediated innate immunity in the small intestine. Best Pract. Res. Clin. Gastroenterol., 2004, v. 18, №2, p. 405–419.Ouellette A. J. Paneth cells and innate mucosal immunity. Curr. Opin. Gastroenterol., 2010, v. 26, p. 547–553.Paneth J. Ueber die secernirenden Zellen des Dünndarm-Epithels. Arch. Mikr. Anat., 1888, Bd. 31, S. 113–191.Parry L., Young M., El Marjou F. and Clarke A. R. Evidence for a crucial role of Paneth cells in mediating the intestinal response to injury. Stem Cells, 2013, v. 31, № 4, p. 776–785Pearse A. G.E. The cytochemistry and ultrastructure of polypeptide hormone producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J. Histochem. Cytochem., 1969, v. 17, 303–313.Peeters T. and Vantrappen G. The Paneth cell: a source of intestinal lysozyme. Gut, 1975, v. 16, p. 553–558.Porter E. M., Bevins C. L., Ghosh D. and Ganz T. The multifaceted Paneth cell. Cell Mol. Life Sci., 2002, v. 59, №1, p. 156– 170.Porter E. M., Liu L., Oren A. et al. Localization of human intestinal defensin 5 in Paneth cell granules. Infect. Immun., 1997, v. 65, p. 2389–2395.Potten C. S. Kinetics and possible regulation of crypt cell populations under normal and stress conditions. Bull. Cancer, 1975, v. 62, 419–430.Potten C. S. Stem cells in gastrointestinal epithelium: numbers, characteristics and death. Philos. Trans. R. Soc. Lond. B Biol. Sci., 1998, v. 353, p. 821–830.Poulsen S. S., Nexø E., Olsen P. S. et al. Immunohistochemical localization of epidermal growth factor in rat and man. Histochemistry, 1986, v. 85, №5, p. 389–394.Przystalski A. The dimension of the mucosa and the structure of the alimentary canal in some reptiles. Acta Biol. Cracoviensia, Ser. Zool., 1980, v. 23, p. 1–33.Qu X. D., Lloyd K. C., Walsh J. H. and Lehrer R. I. Secretion of type II phospholipase A2 and cryptdin by rat small intestinal Paneth cells. Infect. Immun., 1996, v. 64, p. 5161–5165.Riecken E. O. and Pearse A. G.E. Histochemical study on the Paneth cell in the rat. Gut, 1966, v. 7, p. 86–93.Rodning, C. B., Wilson, I. D. and Erlandsen, S. L. Immunoglobulins within human small intestinal Paneth cells. Lancet, 1976, v. 1, p. 984–987.Rumio C., Sommariva M., Sfondrini L. et al. Induction of Paneth cell degranulation by orally administered Toll-like receptor ligands. J. Cell Physiol., 2012, v. 227, №3, p. 1107–1113.Salzman N. H. Paneth cell defensins and the regulation of the microbiome. Detente at mucosal surfaces. Gut Microbes, 2010, v.1, №6, р. 401–406.Salzman N. H., Ghosh D., Huttner K. M. et al. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature, 2003, v. 422, p. 522–526.Sandow M. J. and Whitehead R. The Paneth cell. Gut, 1979, v. 20, p. 420–431.Sato T., van Es J. H., Snippert H. J. et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature, 2011, v. 469, p. 415–418.Satoh Y. Ultrastructure of Paneth cells in germ-free rats, with special reference to the secretory granules and lysosomes. Arch. Histol. Jpn., 1984, v. 47, №3, p. 293–301.Satoh Y. Effect of live and heat-killed bacteria on the secretory activity of Paneth cells in germ-free mice. Cell Tissue Res., 1988, v. 251, p. 87–93.Satoh Y. Atropine inhibits the degranulation of Paneth cells in ex-germ-free mice. Cell Tissue Res., 1988, v. 253, p. 397–402.Satoh Y., Habara Y., Ono K. and Kanno T. Carbamylcholineand catecholamine-induced intracellular calcium dynamics of epithelial cells in mouse ileal crypts. Gastroenterology, 1995, v. 108, p. 1345–1356.Satoh Y., Yamano M., Matsuda M. and Ono K. Ultrastructure of Paneth cells in the intestine of various mammals. J. Electron Microsc. Tech., 1990, v. 16, p. 69–80.Sawada M., Takahashi K., Sawada S. and Midorikawa O. Selective killing of Paneth cells by intravenous administration of dithizone in rats. Int. J. Exp. Pathol., 1991, v. 72, p. 407–421.Schmauder-Chock E. A., Chock S. P. and Patchen M. L. Ultrastructural localization of tumor necrosis factor-α. Histochem. J., 1994, v. 26, p. 142–151Schmidt J. E. Beiträge zur normalen und pathologischen Histologie einiger Zellarten der Schleimhaut des menschlichen Darmkanales. Arch. Mikr. Anat., 1905, Bd. 66, S. 12–40.Schwalbe G. Beiträge zur Kenntniss der Drüsen in der Darmwandungen, in’s Besondere der Brunner’schen Drüsen. Arch. Mikr. Anat., 1872, Bd. 8, S. 92–140.Scott H. and Brandtzaeg P. Enumeration of Paneth cells in coeliac disease: comparison of conventional light microscopy and immunofluorescence staining for lysozyme. Gut, 1981, v. 22, p. 812–816.Scoville D. H., Sato T, He X. C. and Li L. Current view: intestinal stem cells and signaling. Gastroenterology, 2008, v. 134, p. 849–864.Selzman H. M. and Liebelt R. A. A cytochemical analysis of Paneth cell secretion in the mouse. Anat. Rec., 1961, v. 140, p. 17–22.Senegas-Balas F., Balas D., Verger R. et al. Immuno histochemical localization of intestinal phospholipase A2 in rat Paneth cells. Histochemistry, 1984, v. 81, p. 581–584.Seno H., Sawada M., Fukuzawa H. et al. Enhanced expression of transforming growth factor (TGF)-alpha precursor and TGFbeta1 during Paneth cell regeneration. Dig. Dis. Sci., 2001, v. 46, p. 1004–1010.Seno H., Sawada M., Fukuzawa H. et al. Involvement of tumor necrosis factor alpha in intestinal epithelial cell proliferation following Paneth cell destruction. Scand. J. Gastroenterol., 2002, v. 37, 2, p. 154–160.Shaker A. and Rubin D. C. Intestinal stem cells and epithelial-mesenchymal interactions in the crypt and stem cell niche. Transl. Res., 2010, v. 156, №3, p. 180–187.Sheahan D. G. and Jervis H. R. Comparative histochemistry of gastrointestinal mucosubstances. Am. J. Anat., 1976, v. 146, p. 103–131.Shen B., Porter E. M., Reynoso E. et al. Human defensin 5 expression in intestinal metaplasia of the upper gastrointestinal tract. J. Clin. Pathol., 2005, v. 58, p. 687–694.Singh I. The distribution of Paneth cells in the human small intestine. Anat. Anz., 1971, Bd. 128, S. 60–65.Speece A. J. Histochemical distribution of lysozyme activity in organs of normal mice and radiation chimeras. J. Histochem. Cytochem., 1964, v. 12, 384–391.Spicer S. S., Staley M. W., Wetzel M. G. and Wetzel B. K. Acid mucosubstances and basic protein in mouse Paneth cells. J. Histochem. Cytochem., 1967, v. 15, p. 225–242.Stedman’s Medical Eponyms. Ed. S. L. Bartolucci and P. Forbis 2nd edit., Baltimore, Williams and Wilkins, 2005, p. 173.Takahashi N., Vanlaere I., de Rycke R. et al. IL-17 produced by Paneth cells drives TNF-induced shock. J. Exp. Med., 2008, v. 205, p. 1755–1761.Takeda N., Jain R., LeBoeuf M. R. et al. Interconversion between intestinal stem cell populations in distinct niches. Science, 2011, v. 334, p. 1420–1424.Tan X., Hsueh W. and Gonzalez-Crussi F. Cellular localization of tumor necrosis factor (TNF)-alpha transcripts in normal bowel and in necrotizing enterocolitis. TNF gene expression by Paneth cells, intestinal eosinophils, and macrophages. Am. J. Pathol., 1993, v. 142, p. 1858–1865.Tanabe H., Ayabe T., Bainbridge B. et al. Mouse Paneth cell secretory responses to cell surface glycolipids of virulent and attenuated pathogenic bacteria. Infect. Immun., 2005, v. 73, p. 2312–2320.Tanabe H., Sato T., Watari J. et al. Functional role of metaplastic Paneth cell defensins in Helicobacter pylori-infected stomach. Helicobacter, 2008, v. 13, №5, p. 370–379.Tang Q. J., Wang L. M., Tao K. Z. et al. Expression of polymeric immunoglobulin receptor mRNA and protein in human Paneth cells: Paneth cells participate in acquired immunity. Am. J. Gastroenterol., 2006, v. 101, №7, p. 1625–1632.Thrasher J. D. and Greulich R. C. The duodenal progenitor population. III. The progenitor cell cycle of principal, goblet and Paneth cells. J. Exp. Zool., 1966, v. 161, p. 9–19.Tian H., Biehs B., Warming S. et al. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature, 2011, v. 478, p. 255–259.Toner P. G. Cytology of intestinal epithelial cells. Int. Rev. Cytol., 1968, v. 24, p. 233–343.Trier J. S., Lorenzsonn V. and Groehle K. Pattern of secretion of Paneth cells of the small intestine of mice. Gastroenterology, 1967, v. 53, p. 240–249.Troughton W. D. and Trier J. S. Paneth and goblet cell renewal in mouse duodenal crypts. J. Cell Biol., 1969, v. 41, p. 251–268.Vaishnava S., Behrendt C. L. and Ismail A. S. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc. Natl. Acad. Sci. USA, 2008, v. 105, № 52, p. 20858–20863.van der Flier L. G. and Clevers H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu. Rev. Physiol., 2009, v. 71, p. 241–260.van Es J. H., Jay P., Gregorieff A. et al. Wnt signaling induces maturation of Paneth cells in intestinal crypts. Nat. Cell Biol., 2005, v. 7, p. 381–386.Vanuytsel T., Senger S., Fasano A. and Shea-Donohue T. Major signaling pathways in intestinal stem cells. Biochim. Biophys. Acta, 2013, v. 1830, p. 2410–2426.Wang D., Peregrina K., Dhima E. et al. Paneth cell marker expression in intestinal villi and colon crypts characterizes dietary induced risk for mouse sporadic intestinal cancer. Proc. Natl. Acad. Sci. USA, 2011, v. 108, №25, p. 10272–10277.Wehkamp J. and Stange E. F. Paneth’s disease. J. Crohn’s Colitis, 2010, v. 4, p. 523–531.Yan K. S., Chia L. A., Li X. et al. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc. Natl. Acad. Sci. USA, 2012, v. 109, p. 466–471.