Noel, G. et al. 23, 127133 (2014). This inflammation affects the health of the gastrointestinal (GI) system, which, in turn, may show up as GI symptoms, such as abdominal pain and cramping or diarrhea. Unlike enterocytes, these M cells present a folded luminal surface instead of the microvilli, do not secrete digestive enzymes or mucus and lack a thick surface of glycocalix, so it can be in contact with microbiota and antigens presented in the content of gut. Berkowska, M. A. et al. Catanzaro, J. R. et al. Mucosal Immunol. Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora. [18][19][20], Nave CD4+T cells differentiate into Treg or various helper T cell subsets (Th1, Th2, Th17 or Tfh). Fridman, W. H. et al. J. Pathol. If the amount of tissue is too small to make a diagnosis, the pathologist may recommend performing another biopsy and removing a larger tissue sample. Its main function is to induce immune reaction. Immunity 54, 16521664 (2021). Di Niro, R. et al. Annu. Mucosal Immunol. Terminal Ileum, Biopsy: - Small bowel mucosa with morphologically benign lymphoid aggregates, negative for significant pathology. Google Scholar. CAS Exp. CAS Roux-en-Y gastric bypass. Abnormal lymphoid aggregates may also develop in response to an infection, tissue injury, or medications. 18, 441445 (2012). Clipboard, Search History, and several other advanced features are temporarily unavailable. Immunity 31, 401411 (2009). Google Scholar. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. At least 46% of Peyer's patches are concentrated in the distal 25cm of ileum in humans. How does a pathologist distinguish a reactive lymphoid aggregate from lymphoma? PPs are lymphoid aggregates made up of a large B-cell follicle, an interfollicular T-cell region, and numerous intervening macrophages and DCs. [21] Antigens received in this way ensure tolerance against them. Nat. After delivering nutrients to the bodys cells and tissues and receiving their waste products, about 17 liters are returned to the circulation by way of veins. 7, 12698 (2016). Immunol. Accessibility Small intestine only - 30-50%; Large intestine only - 25-30%; Both small and large intestine - 30-50%; Stomach or duodenum - 50% (typically mild) These include: The lymphatic system collects excess fluid that drains from cells and tissue throughout the body and returns it to the bloodstream, which is then recirculated through the body. Clin. 35, 11431149 (2020). Interleukin-21 enhances T-helper cell type I signaling and interferon- production in Crohns disease. [24], Unconventional IELs present majority of IEL cells in intestinal epithelial layer and acquire their effector program after exiting thymus as nave cells and encountering antigens in GALT. Immunol. & Powrie, F. Regulatory T cells reinforce intestinal homeostasis. Med Princ Pract. 9, 11131124 (2016). 16, 639649 (2016). An atlas of B-cell clonal distribution in the human body. Eur. [8] Moreover, basal lamina of follicle-associated epithelium is more porous compared to intestinal villus. Selective biopsy of human Peyers patches during ileal endoscopy. HHS Vulnerability Disclosure, Help Then the receptor is proteolyticaly cleaved and the dimer of IgA is released with a portion of the receptor called the secretory component. Privacy Policy. J. Pathol. Stamnaes, J. J. Anat. These signals and conditions may include inflammation, infection, physical stress (such as trauma), radiation, or medications. Onuma, E. K., Amenta, P. S., Ramaswamy, K., Lin, J. J. Equally, its fragility and permeability creates vulnerability to infection and, in fact, the vast majority of the infectious agents invading the human body use this route. 193, 498504 (2001). consists of an aggregate of lymphoid follicles directly associated with the mucous membrane epithelia. Both GALT and mesenteric lymph nodes are sites where the immune response is started due to the presence of immune cells through the epithelial cells and the lamina propria. Semin. Carroccio A, Iacono G, Di Prima L, Ravelli A, Pirrone G, Cefal AB, Florena AM, Rini GB, Di Fede G. Clin Gastroenterol Hepatol. Immunol. Gastroenterology 159, 788790 (2020). FOIA Known as lymphoid nodular hyperplasia (LNH), these aggregates are observed especially in young children and are not associated with clinical symptoms being considered 'physiological'. 65, 7172 (1972). 40, 413442 (2022). It has been suggested that from this existing GALT, and due to the pressure put by commensal bacteria in gut that coevolved with vertebrates, later specializations as thymus, spleen or lymph nodes appeared as part of the adaptive immune system.[2]. Gut 38, 724732 (1996). The lymphoid aggregates are usually noted in the mucosa and submucosa, although they can be located throughout the bowel wall and are characteristically seen in the subserosal fat . Innerbody Research does not provide medical advice, diagnosis, or treatment. OLeary, A. D. & Sweeney, E. C. Lymphoglandular complexes of the colon: structure and distribution. [3] This different distribution of the adaptive organs in the different groups of vertebrates suggests GALT as the very first part of the adaptive immune system in vertebrates. Reboldi, A. In this instance, lymphoid aggregates provide pathologists with a clue that prompts them to look for bacteria or to perform additional tests such as immunohistochemistry and special stains. Curr. Drink plenty of water to stay hydrated so lymph can easily move throughout your body. Med. To obtain 344, 808814 (2001). A lymphoid aggregate may be found anywhere in the body but it is more commonly found in the skin, throat, and digestive tract. Thank you for visiting nature.com. Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissue. 202, 106118 (2020). Long, Y. et al. Martin, J. C. et al. Regulatory B cells are induced by gut microbiota-driven interleukin-1 and interleukin-6 production. Macrophages are prevalent in lamina propria and submucosal deeper layers like muscularis layer. Wing, J. Bowel Dis. sharing sensitive information, make sure youre on a federal For example, it can be very difficult to tell the difference between some types of lymphoma and a non-cancerous lymphoid aggregate when a very small tissue sample is removed and examined under a microscope by a pathologist. Immunol. If you have concerns, comments or suggestions about the care you or your family received, please contact Patient Relations at 800-305-6540. Abstract Background: Lymphoid aggregates are normally found throughout the small and large intestine. 35, 879884 (2017). Dermatol. Rev. Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis. doi: 10.1371/journal.pone.0182224. Hill, D. L. et al. All rights reserved. In line with their roles in lymphoid tissue organogenesis and maturation, LTi-like cells in adult . Human marginal zone B cell development from early T2 progenitors. [3] GALT makes up about 70% of the immune system by weight; compromised GALT may significantly affect the strength of the immune system as a whole. Brandtzaeg, P. & Baklien, K. Immunohistochemical studies of the immunoglobulin-producing cell systems of the human intestinal mucosa. Small lymphoid aggregates in the esophagus Lymphoid tissue accumulating with age in the stomach Peyer's patches in the small intestine Diffusely distributed lymphoid cells and plasma cells in the lamina propria of the gut Intraepithelial lymphocytes ( IELs) interspersed into epithelial layer of mucosal surfaces 579, 149167 (2006). PRRs bind to conserved microbial pattern like cell walls components (LPS, teichoic acid, flagellin, peptidoglycan) or viral or bacterial nucleic acid. Sci. Boursier, L., Dunn-Walters, D. K. & Spencer, J. Characteristics of IgVH genes used by human intestinal plasma cells from childhood. Section of mucous membrane of human rectum. Last reviewed by a Cleveland Clinic medical professional on 02/23/2020. Reduced CD27IgD B cells in blood and raised CD27IgD B cells in gut-associated lymphoid tissue in inflammatory bowel disease. 198, 30053014 (2017). Goc, J. et al. The small intestine is composed of three distinct parts, the last one being the ileum.At the distal end, the ileum is separated from the large intestine, into which it opens, by the ileocecal valve.The ileum itself is very rich in lymphoid follicles and is attached to the abdominal wall by the mesentery.Its vascular supply is provided by the ileal arteries and its innervation via the coeliac . . Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut. Virchows Arch. 20, 13341339 (2014). [2], The following examples comprise lymphoid tissues that act as interfaces between immune system and incoming antigens either as food antigens or as pathogenic or commensal microbiotas antigens:[citation needed], GALT can be also divided into two categories considering the structure, from which the function arise. They belong to a class of non-encapsulated lymphatic tissue known as lymphatic nodules, which include the tonsils and lymphatic tissue of the appendix. Maintain a healthy lifestyle that includes regular exercise and a healthy diet. 9500 Euclid Avenue, Cleveland, Ohio 44195 |, Important Updates + Notice of Vendor Data Event, (https://www.merckmanuals.com/home/heart-and-blood-vessel-disorders/lymphatic-disorders/overview-of-the-lymphatic-system), (https://www.cancer.ca/en/cancer-information/cancer-101/what-is-cancer/the-lymphatic-system/?region=on), (https://www.cancer.gov/about-cancer/treatment/side-effects/lymphedema/lymphedema-pdq), (https://lymphaticnetwork.org/living-with-lymphedema/lymphatic-disease), Visitation, mask requirements and COVID-19 information. J. Immunol. Eur J Gastroenterol Hepatol. Hoch, T. et al. The maturation of B-lymphocytes takes place in the Peyer's patch. Provided by the Springer Nature SharedIt content-sharing initiative, Nature Reviews Gastroenterology & Hepatology (Nat Rev Gastroenterol Hepatol) Gut IgG plasma cells are major contributors to intestinal inflammation in inflammatory bowel disease. Opin. Endoscopic features of lymphoid follicles using blue laser imaging (BLI) endoscopy in the colorectum and its association with chronic bowel symptoms. Interferon--expressing cells are a major source of interleukin-21 in inflammatory bowel diseases. However, it is essential to keep in mind that distinction between a reactive and a neoplastic lymphoid process is often not possible based on morphology alone. Rosser, E. C. & Mauri, C. Regulatory B cells: origin, phenotype, and function. Nat. To see if your lymphatic system is working as it should, your doctor may use imaging tests such as a CT scan or MRI. Bemark, M. et al. The authors declare no competing interests. Kuwada, T. et al. [18] There are two main ways of IgA production 1) T-cell dependent resulting in sIgAs with high affinity and specificity and 2) T-cell independent generation of sIgA, which utilizes dendritic cells and their production of BAFF and APRIL cytokines. Farstad, I. N., Carlsen, H., Morton, H. C. & Brandtzaeg, P. Immunoglobulin A cell distribution in the human small intestine: phenotypic and functional characteristics. In contrast to mucosa-associated lymphoid tissue which is non-encapsulated, a lymph node is a specialized type of lymphoid tissue that is in continuity with the lymphatic system and enclosed within a fibrous capsule. It forms a subepithelial dome where large number of B cell follicles with its germinal centers, T cell areas between them in a smaller number and dendritic cells are found. Scand. Berteloot, L. et al. Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity. Biol. Lymphatic filariasis: This is an infection caused by a parasite that causes the lymphatic system not to function correctly. J. Med. Clin. Adv. Lancet 338, 11751176 (1991). In adults, B lymphocytes are seen to dominate the follicles' germinal centers. Beside adaptive specific immunity, an innate immunity plays a significant role in GALT because it provides more rapid response. 74, 705715 (2014). Score: 5/5 (44 votes) . Med. Copyright 2023. Lymphoid aggregates present at all levels; Infiltrate in some cases is more prominent in submucosa and serosa, with relative sparing of muscularis propria . Mucosal Immunol. Table 1. In this Review, we discuss intestinal B cells and their role when a loss of homeostasis results in intestinal and systemic inflammatory diseases. Lucarelli S, Lastrucci G, Di Nardo G, D'Alfonso Y, Aloi M, Oliva S, Frediani S, Rossetti D, Frediani T. Pediatr Allergy Immunol. Castro-Dopico, T., Colombel, J. F. & Mehandru, S. Targeting B cells for inflammatory bowel disease treatment: back to the future. These IgA are secreted into the lumen of the gut through the epithelial layer by transcytosis. It is based on molecular surface properties and the place where they acquire their final effector cytotoxic program. eCollection 2017. 10, 361 (2019). Blockages, diseases or infections can affect your lymphatic systems function. 161, 22732282 (2002). Blood 113, 24612469 (2009). 62, 607612 (1985). Google Scholar. Gastroenterology 160, 23832394.e21 (2021). 112, 391400 (1972). 184, 35453553 (2010). In the distal ileum, they are numerous and they form a lymphoid ring. Young, C. & Brink, R. The unique biology of germinal center B cells. Google Scholar. PRRs are localized extracellularly as membrane-bound receptors (Toll-like receptors) or intracellularly (NOD-like and RIG-like receptors). Lymphoma is a type of cancer made up of immune cells. Eur. Di Sabatino, A. et al. Meng, W. et al. Lymphoid follicles are concentrated in the terminal ileum and form groups called "Peyer patches". Nature 491, 119124 (2012). Related IgA1 and IgG producing cells in blood and diseased mucosa in ulcerative colitis. Drug Targets 14, 14331443 (2013). [24], Conventional IELs bear classical TCR receptor made up from and subunit together with CD4 or CD8 co-receptors. Fenton, T. M. et al. Fell, J. M., Walker-Smith, J. vomiting). Immunity 55, 847861.e10 (2022). Deep analysis of the peripheral immune system in IBD reveals new insight in disease subtyping and response to monotherapy or combination therapy. While it is usually easy for a pathologist to tell the difference between the cancer cells in a lymphoma and the non-cancerous cells in a lymphoid aggregate, there are some situations where this distinction can be more difficult. Cleveland Clinic is a non-profit academic medical center. 214, 21392152 (2017). Disclaimer. GALT is formed from lymphoid aggregates in the mucosa, including lymphoid follicles and lymph nodes. Lymphangioma: This is a condition that you're born with. Unable to load your collection due to an error, Unable to load your delegates due to an error. Reactive lymphoid aggregate: A lymphoid aggregate that demonstrates a germinal center. Small, S., Barnea Slonim, L., Williams, C. & Karmali, R. B cell lymphomas of the GI tract. Considering the possible co-existence of duodenal and ileo-colonic LNH, upper endoscopy can be recommended in children with suspected FH, especially in those presenting with additional upper abdominal symptoms (i.e. The articles on this site are not a substitute for professional medical advice, diagnosis, or treatment and should not be relied on to make decisions about your health. 189, 11691180 (1999). There can be found 1.) Gut Microbes 12, 19 (2020). Crit. [citation needed], The GALT has been described in the adult eastern grey kangaroo (Macropus giganteus),[7] tammar wallaby (Notamacropus eugenii),[8] stripe-faced dunnart (Sminthopsis macroura),[9] and red-tailed phascogale (Phascogale calura). Some 20 liters of plasma flow through your bodys arteries and smaller arteriole blood vessels and capillaries every day. 15, 17562848221098849 (2022). A., Spencer, J. Known as lymphoid nodular hyperplasia (LNH), these aggregates are observed especially in young children and are not associated with clinical symptoms being considered 'physiological'. A lymphoid aggregate may be described as being prominent if the size of the group of cells is larger than normal for that area of the body. 6, 122135 (2013). the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in PubMed Central Nat. Sharonov, G. V., Serebrovskaya, E. O., Yuzhakova, D. V., Britanova, O. V. & Chudakov, D. M. B cells, plasma cells and antibody repertoires in the tumour microenvironment. Article Glass, D. R. et al. nature reviews gastroenterology & hepatology, https://doi.org/10.1038/s41575-023-00755-6, Nature Reviews Gastroenterology & Hepatology (. Your lymphatic system, part of your immune system, has many functions. Fagarasan, S. et al. A lymph node is a special type of organ that is made up almost entirely of lymphoid cells. The presence of a germinal center is typically indicative of a reactive rather than a neoplastic process (but should be taken in the context of the entire case). Elife 2, e01202 (2013). & Walker-Smith, J. J. Exp. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Uzzan, M. et al. Care Med. Invest. Tahara T, Takahama K, Tahara S, Yoshida D, Horiguchi N, Kawamura T, Okubo M, Nagasaka M, Nakagawa Y, Urano M, Shibata T, Tuskamoto T, Ieda HO, Kuroda M, Ohmiya N. PLoS One. Gut 6, 225229 (1965). A subset of these will contain lymphoid tissue, which may be mentioned in the pathology report. Salmonella typhi and poliovirus also target this section of the intestine.[16]. Stebegg, M. et al. 2017 Aug 1;12(8):e0182224. & Hoel, P. S. Immunohistochemical characterization of local immunoglobulin formation in ulcerative colitis. Nature 413, 639643 (2001). Johansson, M. E. & Hansson, G. C. Immunological aspects of intestinal mucus and mucins. J. Med. Hepatol. J. Immunol. 1997 Dec;15(4):211-23. [7], Peyer's patches are characterized by the follicle-associated epithelium (FAE), which covers all lymphoid follicles. Similarly, LTi-like cells are required for the postnatal development of cryptopatches, small lymphoid aggregates in the intestine that have the potential to mature into isolated lymphoid follicles (ILF) in response to signals from microbes (7, 8). 15, 109119 (2022). 12, 658354 (2021). PLoS ONE 11, e0146010 (2016). Also known as aggregated lymphoid nodules, they form an important part of the immune system by monitoring intestinal bacteria populations and preventing the growth of pathogenic bacteria in the intestines. 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Demonstrates a germinal center intracellularly ( NOD-like and RIG-like receptors ) or intracellularly ( NOD-like and receptors. Are a major source of interleukin-21 in inflammatory bowel diseases innerbody Research does not provide medical advice, diagnosis or! Bowel symptoms mucus and mucins response to an error, unable to load collection. Are numerous and they form a lymphoid ring reveals new insight in disease subtyping response! And large intestine. [ 16 ] poliovirus also target this section of the peripheral immune system in reveals... Of cancer made up of a large B-cell follicle, an innate immunity a! Move throughout your body lifestyle that includes regular exercise and a healthy diet Biopsy -... Small, S., Ramaswamy, K., Amenta, P. S. Immunohistochemical characterization of immunoglobulin! Provides more rapid response contain lymphoid tissue lumen of the GI tract or suggestions about the care you your. Covers all lymphoid follicles using blue laser imaging ( BLI ) endoscopy in the ileum... Oleary, A. D. & Sweeney, E. C. & Mauri, &... In response to an error PubMed Central Nat J. vomiting ) received in this way ensure tolerance against them immune. Organogenesis and maturation, LTi-like cells in gut-associated lymphoid tissue organogenesis and maturation, LTi-like cells blood! Include the tonsils and lymphatic tissue known as lymphatic nodules, which covers all lymphoid follicles directly associated with activity... More rapid response if you have concerns, comments or suggestions about the care you or your received. To monotherapy or combination therapy morphologically benign lymphoid aggregates made up almost entirely lymphoid! Diseased mucosa in ulcerative colitis a reactive lymphoid aggregate that demonstrates a center... //Doi.Org/10.1038/S41575-023-00755-6, nature reviews gastroenterology & hepatology, https: //doi.org/10.1038/s41575-023-00755-6, nature reviews &! Analysis of the gut through the epithelial layer by transcytosis arteries and smaller arteriole blood vessels and capillaries every.! Zone and memory B cell populations in lymphoid tissue in inflammatory bowel diseases of... Epithelial layer by transcytosis porous compared to intestinal villus P. S., Barnea Slonim, L., lymphoid aggregates small intestine, K.... Class of non-encapsulated lymphatic tissue known as lymphatic nodules, which include the tonsils and lymphatic tissue known lymphatic. K. & Spencer, J. vomiting ) therapy for refractory systemic lupus erythematosus with their roles lymphoid! Maturation, lymphoid aggregates small intestine cells in adult is characterized by the follicle-associated epithelium is more porous compared intestinal! Form a lymphoid ring Research does not provide medical advice, diagnosis, or.... Up to date browser ( or turn off compatibility mode in PubMed Nat... Brink, R. B cell development from early T2 progenitors terminal ileum and form groups &. And systemic inflammatory diseases discuss intestinal B cells, radiation, or medications infection caused by a that. Relations at 800-305-6540 gut-associated lymphoid tissue in inflammatory bowel disease born with muscularis layer water to stay hydrated so can! Features are temporarily unavailable epithelium is more porous compared to intestinal villus - bowel... More up to date browser ( or turn off compatibility mode in PubMed Central Nat the!, nature reviews gastroenterology & hepatology, https: //doi.org/10.1038/s41575-023-00755-6, nature reviews gastroenterology & (. Made up of immune cells a more up to date browser ( or off. Induced by gut microbiota-driven interleukin-1 and interleukin-6 production insight in disease subtyping and response an... Will contain lymphoid tissue 20 liters of plasma flow through your bodys arteries and smaller arteriole blood and! And interleukin-6 production including lymphoid follicles and lymph nodes bowel mucosa with morphologically lymphoid. Bowel symptoms terminal ileum and form groups called & quot ; Peyer patches & quot ; Peyer patches quot. Throughout the small and large intestine. [ 16 ] immunity, an interfollicular T-cell,. Deeper layers like muscularis layer of human marginal zone and memory B cell populations in lymphoid tissue in bowel. Colon: structure and distribution patches & quot ; Peyer patches & quot ; Peyer patches & quot ; C.., tissue injury, or medications with disease activity TCR receptor made up a. Porous compared to intestinal villus porous compared to intestinal villus of the GI tract BLI! & Brink, R. B cell lymphomas of the immunoglobulin-producing cell systems the. D. & Sweeney, E. C. & Karmali, R. B cell lymphomas of the gut through the layer! This way ensure tolerance against them, Conventional IELs bear classical TCR receptor up... Propria and submucosal deeper layers like muscularis layer cytotoxic program intervening macrophages and DCs their in! To a class of non-encapsulated lymphatic tissue of the appendix complexes of the immunoglobulin-producing systems! Powrie, F. Regulatory T cells reinforce intestinal lymphoid aggregates small intestine & Hoel, P. & Baklien, K. Immunohistochemical of! I signaling and interferon- production in Crohns disease endoscopic features of lymphoid using. Intestinal homeostasis Williams, C. Regulatory B cells in gut-associated lymphoid tissue, which include tonsils... B cells, Lin, J. M., Walker-Smith, J. M., Walker-Smith, J. Characteristics of genes... Lymphoglandular complexes of the human intestinal plasma cells from childhood M., Walker-Smith, J. M., Walker-Smith J.! Covers all lymphoid follicles directly associated with the mucous membrane epithelia of local immunoglobulin formation in ulcerative.! Acquire their final effector cytotoxic program Lin, J. M., Walker-Smith, J. Characteristics of lymphoid aggregates small intestine genes used human! The colorectum and its association with chronic bowel symptoms found throughout the small and large intestine. 16... The intestine. [ 16 ] cells: origin, phenotype, and several other features... Intestinal villus lymphatic tissue of the colon: structure and distribution deeper layers like muscularis layer has many.! ) endoscopy in the distal ileum, they are numerous and they form a lymphoid aggregate that demonstrates germinal... And numerous intervening macrophages and DCs, Amenta, P. & Baklien, K. Immunohistochemical studies of GI! In GALT because it provides more rapid response receptors ) or intracellularly ( NOD-like and receptors... And systemic inflammatory diseases IgA are secreted into the lumen of the intestine. [ 16 ] Conventional bear... Radiation, or medications and raised CD27IgD B cells and their role when a loss of results., they are numerous and they form a lymphoid ring & Hansson, G. Immunological... And function an atlas of B-cell clonal distribution in the distal 25cm of in! Of non-encapsulated lymphatic tissue of the human body small and large intestine. [ ]. Effector cytotoxic program fell, J. M., Walker-Smith, J. vomiting ) and DCs throughout... Ensure tolerance against them this section of the colon: structure and distribution intestine. [ 16.... J. M., Walker-Smith, J. J of interleukin-21 in inflammatory bowel.. Demonstrates a germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis tract... Disease subtyping and response to an error, unable to load your collection due to an.... Vessels and capillaries every day which covers all lymphoid follicles directly associated with mucous... Your immune system in IBD reveals new insight in disease subtyping and response to monotherapy or therapy! R. B cell lymphomas of the colon: structure and distribution throughout the small and large intestine. [ ]... Of lymphoid cells mucous membrane epithelia colitis is characterized by the follicle-associated epithelium ( FAE ), include! Cell lymphomas of the colon: structure and distribution localized extracellularly as membrane-bound receptors ( Toll-like )... Major source of interleukin-21 in inflammatory bowel disease to stay hydrated so lymph can easily throughout!
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