The Role of the Lymphatic System in the Pathogenesis and Treatment of Inflammatory Bowel Disease

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Feb 15

PMID 35163775

Authors

Dimitrios Nikolakis

Floris A E de Voogd

Maarten J Pruijt

Joep Grootjans

Marleen G van de Sande

Geert R DHaens

Affiliations

Soon will be listed here.

Abstract

Although the number of therapeutic options for the treatment of inflammatory bowel disease (IBD) has increased in recent years, patients suffer from decreased quality of life due to non-response or loss of response to the currently available treatments. An increased understanding of the disease's etiology could provide novel insights for treatment strategies in IBD. Lymphatic system components are generally linked to immune responses and presumably related to inflammatory diseases pathophysiology. This review aims to summarize findings on immune-mediated mechanisms in lymphoid tissues linked with IBD pathogenesis and (potential) novel treatments. Enhanced innate and adaptive immune responses were observed in mesenteric lymph nodes (MLNs) and other lymphoid structures, such as Peyer's patches, in patients with IBD and in animal models. Furthermore, the phenomenon of lymphatic obstruction in the form of granulomas in MLNs and lymphatic vessels correlates with disease activity. There is also evidence that abnormalities in the lymphatic stromal components and lymph node microbiome are common in IBD and could be exploited therapeutically. Finally, novel agents targeting lymphocyte trafficking have been added to the treatment armamentarium in the field of IBD. Overall, gut-associated lymphoid tissue plays a key role in IBD immunopathogenesis, which could offer novel therapeutic targets.

Citing Articles

Mesenteric Lymphatic B Cells Migrate to the Intestine and Aggravate DSS-Induced Colitis via the CXCR5-CXCL13 Axis.

Zhang Y, Wu Z, Zhao Q, Liu Y, Huang Q, Zhang M Biology (Basel). 2024; 13(5).

PMID: 38785804 PMC: 11117591. DOI: 10.3390/biology13050322.

Morphofunctional Alteration of Mesenteric Lymph Nodes in the Inflammation of the Abdominal Cavity.

Abdreshov S, Demchenko G, Yeshmukhanbet A, Yessenova M, Mankibaeva S, Atanbaeva G Biology (Basel). 2024; 13(3).

PMID: 38534436 PMC: 10967999. DOI: 10.3390/biology13030166.

Crohn's disease as the intestinal manifestation of pan-lymphatic dysfunction: An exploratory proposal based on basic and clinical data.

Zhou Y, Ren Y, Lu M, Xu L, Cheng W, Zhang M World J Gastroenterol. 2024; 30(1):34-49.

PMID: 38293325 PMC: 10823898. DOI: 10.3748/wjg.v30.i1.34.

Multiple mesenteric lymphadenopathies in pediatric with ulcerative colitis: A case report.

Ratih S, Makrufardi F, Azizah A, Damayanti W Radiol Case Rep. 2023; 19(2):600-603.

PMID: 38074434 PMC: 10709117. DOI: 10.1016/j.radcr.2023.10.046.

Delivery Strategies of Probiotics from Nano- and Microparticles: Trends in the Treatment of Inflammatory Bowel Disease-An Overview.

Lopes S, Roque-Borda C, Duarte J, Di Filippo L, Cardoso V, Pavan F Pharmaceutics. 2023; 15(11).

PMID: 38004578 PMC: 10674632. DOI: 10.3390/pharmaceutics15112600.

References

Mann E, Bernardo D, Ng S, Rigby R, Al-Hassi H, Landy J . Human gut dendritic cells drive aberrant gut-specific t-cell responses in ulcerative colitis, characterized by increased IL-4 production and loss of IL-22 and IFNγ. Inflamm Bowel Dis. 2014; 20(12):2299-307. DOI: 10.1097/MIB.0000000000000223. View

Philpott J, Miner Jr P . Antisense inhibition of ICAM-1 expression as therapy provides insight into basic inflammatory pathways through early experiences in IBD. Expert Opin Biol Ther. 2008; 8(10):1627-32. DOI: 10.1517/14712598.8.10.1627. View

Miner Jr P, Wedel M, Xia S, Baker B . Safety and efficacy of two dose formulations of alicaforsen enema compared with mesalazine enema for treatment of mild to moderate left-sided ulcerative colitis: a randomized, double-blind, active-controlled trial. Aliment Pharmacol Ther. 2006; 23(10):1403-13. DOI: 10.1111/j.1365-2036.2006.02837.x. View

Bandinelli F, Milia A, Manetti M, Lastraioli E, D Amico M, Tonelli P . Lymphatic endothelial progenitor cells and vascular endothelial growth factor-C in spondyloarthritis and Crohn's disease: two overlapping diseases?. Clin Exp Rheumatol. 2015; 33(2):195-200. View

Karuppuchamy T, Behrens E, Gonzalez-Cabrera P, Sarkisyan G, Gima L, Boyer J . Sphingosine-1-phosphate receptor-1 (S1P) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease. Mucosal Immunol. 2016; 10(1):162-171. PMC: 5053832. DOI: 10.1038/mi.2016.35. View

Pararasa C, Zhang N, Tull T, Chong M, Siu J, Guesdon W . Reduced CD27IgD B Cells in Blood and Raised CD27IgD B Cells in Gut-Associated Lymphoid Tissue in Inflammatory Bowel Disease. Front Immunol. 2019; 10:361. PMC: 6411645. DOI: 10.3389/fimmu.2019.00361. View

Dickerson L, De Freitas S, Pozo M, Safar B . Letter to the Editor: Mesenteric Lymphatic Vessel Density Is Associated with Disease Behavior and Postoperative Recurrence in Crohn's Disease. J Gastrointest Surg. 2018; 23(1):181-182. DOI: 10.1007/s11605-018-3987-3. View

Cai Z, Zhang W, Li M, Yue Y, Yang F, Yu L . TGF-beta1 gene-modified, immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4(+)Foxp3(+) regulatory T cells. Cell Mol Immunol. 2010; 7(1):35-43. PMC: 4003258. DOI: 10.1038/cmi.2009.107. View

Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg R, Bhan A . Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity. 2002; 16(2):219-30. DOI: 10.1016/s1074-7613(02)00274-1. View

10.

Feagan B, Sandborn W, DHaens G, Lee S, Allez M, Fedorak R . Randomised clinical trial: vercirnon, an oral CCR9 antagonist, vs. placebo as induction therapy in active Crohn's disease. Aliment Pharmacol Ther. 2015; 42(10):1170-81. DOI: 10.1111/apt.13398. View

11.

Cook M . The size and histological appearances of mesenteric lymph nodes in Crohn's disease. Gut. 1972; 13(12):970-2. PMC: 1412498. DOI: 10.1136/gut.13.12.970. View

12.

Grainger J, Konkel J, Zangerle-Murray T, Shaw T . Macrophages in gastrointestinal homeostasis and inflammation. Pflugers Arch. 2017; 469(3-4):527-539. PMC: 5362667. DOI: 10.1007/s00424-017-1958-2. View

13.

OBrien C, Pavli P, Gordon D, Allison G . Detection of bacterial DNA in lymph nodes of Crohn's disease patients using high throughput sequencing. Gut. 2014; 63(10):1596-606. DOI: 10.1136/gutjnl-2013-305320. View

14.

Cui Y, Lu S, Xu J, Peng Y, Miao Q, Wang X . Microscopic features of small bowel mucosa of patients with Crohn's disease. BMC Gastroenterol. 2020; 19(1):232. PMC: 6937864. DOI: 10.1186/s12876-019-1138-2. View

15.

Loftus Jr E, Feagan B, Panaccione R, Colombel J, Sandborn W, Sands B . Long-term safety of vedolizumab for inflammatory bowel disease. Aliment Pharmacol Ther. 2020; 52(8):1353-1365. PMC: 7540482. DOI: 10.1111/apt.16060. View

16.

Feng T, Qin H, Wang L, Benveniste E, Elson C, Cong Y . Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production. J Immunol. 2011; 186(11):6313-8. PMC: 3249225. DOI: 10.4049/jimmunol.1001454. View

17.

van Deventer S, Tami J, Wedel M . A randomised, controlled, double blind, escalating dose study of alicaforsen enema in active ulcerative colitis. Gut. 2004; 53(11):1646-51. PMC: 1774281. DOI: 10.1136/gut.2003.036160. View

18.

Mizushima T, Ito T, Kishi D, Kai Y, Tamagawa H, Nezu R . Therapeutic effects of a new lymphocyte homing reagent FTY720 in interleukin-10 gene-deficient mice with colitis. Inflamm Bowel Dis. 2004; 10(3):182-92. DOI: 10.1097/00054725-200405000-00002. View

19.

Saha C, Nigam S, Denker B . Involvement of Galphai2 in the maintenance and biogenesis of epithelial cell tight junctions. J Biol Chem. 1998; 273(34):21629-33. DOI: 10.1074/jbc.273.34.21629. View

20.

Sans M, Panes J, Ardite E, Elizalde J, Arce Y, Elena M . VCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis. Gastroenterology. 1999; 116(4):874-83. DOI: 10.1016/s0016-5085(99)70070-3. View