Volume 9 Number 1 2025
Potential Therapeutic Targets Associated with the Autoimmune Response in Crohn's Disease
Alexander V. Blagov1*, Marina D. Sazonova 1, Anastasia I. Ryzhkova1, Vasily P. Karagodin5, Mikhail A. Popov6, Egor Yu. Budnikov1, Alessio Luigi Ravani4, Alexander N. Orekhov1,4, Margarita A. Sazonova1,2, Yuri V. Arkhipenko1,3
Integrative Biomedical Research 9 (1) 1-15 https://doi.org/10.25163/biomedical.9110392
Submitted: 01 September 2025 Revised: 26 October 2025 Accepted: 22 October 2025 Published: 28 October 2025
Abstract
Crohn's disease (CD) represents a chronic inflammatory bowel disorder characterized by complex autoimmune mechanisms that contribute to persistent intestinal inflammation and tissue damage. The pathogenesis involves dysregulated immune responses, including aberrant T-cell activation, cytokine imbalances, and compromised barrier function. This review examines the autoimmune components of CD pathophysiology and identifies promising therapeutic targets for intervention. Key pathways include TNF- α signaling, IL-23/Th17 axis, JAK-STAT pathways, and integrin-mediated leukocyte trafficking. Understanding the pathological functions of proteins involved in these molecular pathways is a prerequisite for identifying new potential therapeutic targets associated with the development of Crohn's disease. Emerging targets such as TL1A, SMAD7, and microRNA regulation offer novel therapeutic opportunities. Current limitations include patient heterogeneity, incomplete understanding of disease mechanisms, and challenges in personalized treatment selection. Future directions emphasize precision medicine approaches, combination therapies, and biomarker development for improved patient stratification. Understanding autoimmune mechanisms in CD provides a foundation for developing more effective, targeted therapeutic interventions that may improve patient outcomes and quality of life.
Keywords: Crohn’s disease, autoimmune pathways, cytokine regulation, therapeutic targets, precision medicine
References
Abraham, C., & Cho, J. H. (2009). Inflammatory bowel disease. New England Journal of Medicine, 361(21), 2066–2078. https://doi.org/10.1056/NEJMra0804647
Ananthakrishnan, A. N. (2015). Epidemiology and risk factors for IBD. Nature Reviews Gastroenterology & Hepatology, 12(4), 205–221. https://doi.org/10.1038/nrgastro.2015.34
Bain, C. C., & Mowat, A. M. (2014). Macrophages in intestinal homeostasis and inflammation. Immunological Reviews, 260(1), 102–117. https://doi.org/10.1111/imr.12192
Bamias, G., Mishina, M., Nyce, M., Ross, W. G., Kollias, G., Rivera-Nieves, J., ... & Cominelli, F. (2006). Role of TL1A and its receptor DR3 in two models of chronic murine ileitis. Proceedings of the National Academy of Sciences, 103(22), 8441–8446. https://doi.org/10.1073/pnas.0510903103
Banchereau, J., & Steinman, R. M. (1998). Dendritic cells and the control of immunity. Nature, 392(6673), 245–252. https://doi.org/10.1038/32588
Ben-Horin, S., & Chowers, Y. (2011). Review article: Loss of response to anti-TNF treatments in Crohn's disease. Alimentary Pharmacology & Therapeutics, 33(9), 987–995. https://doi.org/10.1111/j.1365-2036.2011.04612.x
Berlin, C., Berg, E. L., Briskin, M. J., Andrew, D. P., Kilshaw, P. J., Holzmann, B., ... & Butcher, E. C. (1993). α4β7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell, 74(1), 185–195. https://doi.org/10.1016/0092-8674(93)90305-A
Billiet, T., Rutgeerts, P., Ferrante, M., Van Assche, G., & Vermeire, S. (2014). Targeting TNF-α for the treatment of inflammatory bowel disease. Expert Opinion on Biological Therapy, 14(1), 75–101. https://doi.org/10.1517/14712598.2014.858695
Boivin, G. P., Washington, K., Yang, K., Ward, J. M., Wood, G. A., Gorelick, F. S., ... & Coffey, R. J. (2003). Pathology of mouse models of intestinal cancer: Consensus report and recommendations. Gastroenterology, 124(3), 762–777. https://doi.org/10.1053/gast.2003.50094
Bossuyt, P. M., Reitsma, J. B., Bruns, D. E., Gatsonis, C. A., Glasziou, P. P., Irwig, L. M., ... & de Vet, H. C. (2003). The STARD statement for reporting studies of diagnostic accuracy: Explanation and elaboration. Annals of Internal Medicine, 138(1), W1–W12. https://doi.org/10.7326/0003-4819-138-1-200301070-00010
Brand, S., Beigel, F., Olszak, T., Zitzmann, K., Eichhorst, S. T., Otte, J. M., ... & Ochsenkühn, T. (2006). IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. American Journal of Physiology-Gastrointestinal and Liver Physiology, 290(4), G827–G838. https://doi.org/10.1152/ajpgi.00513.2005
Burke, J. P., Mulsow, J. J., O'Keane, C., Dochery, N. G., Watson, R. W., & O'Connell, P. R. (2007). Fibrogenesis in Crohn's disease. American Journal of Gastroenterology, 102(2), 439–448. https://doi.org/10.1111/j.1572-0241.2006.01010.x
Camilleri, M., Madsen, K., Spiller, R., Greenwood-Van Meerveld, B., & Verne, G. N. (2012). Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterology & Motility, 24(6), 503–512. https://doi.org/10.1111/j.1365-2982.2012.01921.x
Chen, Y., Ge, W., Xu, L., Qu, C., Zhu, M., Zhang, W., & Xiao, Y. (2009). miR-200b is involved in intestinal fibrosis of Crohn's disease. International Journal of Molecular Medicine, 29(4), 601–606. https://doi.org/10.3892/ijmm.2012.894
Colombel, J. F., Sandborn, W. J., Rutgeerts, P., Enns, R., Hanauer, S. B., Panaccione, R., ... & Pollack, P. F. (2007). Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: The CHARM trial. Gastroenterology, 132(1), 52–65. https://doi.org/10.1053/j.gastro.2006.11.041
Colombel, J. F., Sandborn, W. J., Reinisch, W., Mantzaris, G. J., Kornbluth, A., Rachmilewitz, D., ... & Rutgeerts, P. (2010). Infliximab, azathioprine, or combination therapy for Crohn's disease. New England Journal of Medicine, 362(15), 1383–1395. https://doi.org/10.1056/NEJMoa0904492
Colombel, J. F., Narula, N., & Peyrin-Biroulet, L. (2017). Management of Crohn's disease: The current state of the art. Nature Reviews Gastroenterology & Hepatology, 14(6), 352–362.
Danese, S., Vuitton, L., & Peyrin-Biroulet, L. (2015). Biologic agents for IBD: Practical insights. Nature Reviews Gastroenterology & Hepatology, 12(9), 537–545. https://doi.org/10.1038/nrgastro.2015.135
de Souza, H. S., & Fiocchi, C. (2016). Immunopathogenesis of IBD: Current state of the art. Nature Reviews Gastroenterology & Hepatology, 13(1), 13–27. https://doi.org/10.1038/nrgastro.2015.186
Duerr, R. H., Taylor, K. D., Brant, S. R., Rioux, J. D., Silverberg, M. S., Daly, M. J., ... & Cho, J. H. (2006). A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science, 314(5804), 1461–1463. https://doi.org/10.1126/science.1135245
Dulai, P. S., Sandborn, W. J., & Gupta, S. (2016). Colorectal cancer and dysplasia in inflammatory bowel disease: A review of disease epidemiology, pathophysiology, and management. Cancer Prevention Research, 9(12), 887–894. https://doi.org/10.1158/1940-6207.CAPR-16-0124
Feagan, B. G., Rutgeerts, P., Sands, B. E., Hanauer, S., Colombel, J. F., Sandborn, W. J., ... & Milch, C. (2013). Vedolizumab as induction and maintenance therapy for ulcerative colitis. New England Journal of Medicine, 369(8), 699–710. https://doi.org/10.1056/NEJMoa1215734
Feagan, B. G., Sandborn, W. J., Gasink, C., Jacobstein, D., Lang, Y., Friedman, J. R., ... & Tyrrell, H. (2016). Ustekinumab as induction and maintenance therapy for Crohn's disease. New England Journal of Medicine, 375(20), 1946–1960. https://doi.org/10.1056/NEJMoa1602773
Feagan, B. G., Sands, B. E., Rossiter, G., Li, X., Usiskin, K., Zhan, X., & Colombel, J. F. (2018). Effects of mongersen (GED-0301) on endoscopic and clinical outcomes in patients with active Crohn's disease. Gastroenterology, 154(1), 61–64. https://doi.org/10.1053/j.gastro.2017.08.035
Flier, S. N., Tanjore, H., Kokkotou, E. G., Sugimoto, H., Zeisberg, M., & Kalluri, R. (2010). Identification of epithelial to mesenchymal transition as a novel source of fibroblasts in intestinal fibrosis. Journal of Biological Chemistry, 285(26), 20202–20212. https://doi.org/10.1074/jbc.M110.102012
Gilbert, J. A., Blaser, M. J., Caporaso, J. G., Jansson, J. K., Lynch, S. V., & Knight, R. (2018). Current understanding of the human microbiome. Nature Medicine, 24(4), 392–400. https://doi.org/10.1038/nm.4517
Hampe, J., Franke, A., Rosenstiel, P., Till, A., Teuber, M., Huse, K., ... & Schreiber, S. (2007). A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nature Genetics, 39(2), 207–211. https://doi.org/10.1038/ng1954
Hanauer, S. B., Feagan, B. G., Lichtenstein, G. R., Mayer, L. F., Schreiber, S., Colombel, J. F., ... & Pollack, P. F. (2002). Maintenance infliximab for Crohn's disease: The ACCENT I randomised trial. Lancet, 359(9317), 1541–1549. https://doi.org/10.1016/S0140-6736(02)08512-4
Hart, A. L., Al-Hassi, H. O., Rigby, R. J., Bell, S. J., Emmanuel, A. V., Knight, S. C., ... & Stagg, A. J. (2005). Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology, 129(1), 50–65. https://doi.org/10.1053/j.gastro.2005.05.013
Hirano, A., Yamazaki, R., Suzuki, K., Naganuma, M., Ogata, H., & Kanai, T. (2019). Neutralization of TL1A (TNFSF15) attenuates experimental intestinal inflammation via regulation of lamina propria CD4+ T cell function. PLoS One, 14(6), e0218096. https://doi.org/10.1371/journal.pone.0218096
Hugot, J. P., Chamaillard, M., Zouali, H., Lesage, S., Cézard, J. P., Belaiche, J., ... & Thomas, G. (2001). Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature, 411(6837), 599–603. https://doi.org/10.1038/35079107
Iwata, M., Hirakiyama, A., Eshima, Y., Kagechika, H., Kato, C., & Song, S. Y. (2004). Retinoic acid imprints gut-homing specificity on T cells. Immunity, 21(4), 527–538. https://doi.org/10.1016/j.immuni.2004.08.011
Johansson, M. E., Sjövall, H., & Hansson, G. C. (2013). The gastrointestinal mucus system in health and disease. Nature Reviews Gastroenterology & Hepatology, 10(6), 352–361. https://doi.org/10.1038/nrgastro.2013.35
Jostins, L., Ripke, S., Weersma, R. K., Duerr, R. H., McGovern, D. P., Hui, K. Y., ... & Cho, J. H. (2012). Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature, 491(7422), 119–124.
Kamada, N., Hisamatsu, T., Okamoto, S., Chinen, H., Kobayashi, T., Sato, T., ... & Hibi, T. (2008). Unique CD14? intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-γ axis. Journal of Clinical Investigation, 118(6), 2269–2280. https://doi.org/10.1172/JCI34610
Kapasi, R., Glatter, J., Lamb, C. A., Achkar, J. P., Stappenbeck, T., & Jacobs, J. P. (2016). Targeted proteomics of cecum and proximal colon mucosa identifies biomarkers associated with inflammation in pediatric inflammatory bowel disease. Inflammatory Bowel Diseases, 22(6), 1266–1274.
Katlinskaya, Y. V., Katlinski, K. V., Lasri, A., Li, N., Beiting, D. P., Durham, A. C., ... & Fuchs, S. Y. (2016). Type I interferon signaling regulates the magnitude and chronicity of colitis. Cell Reports, 14(4), 897–909.
Khor, B., Gardet, A., & Xavier, R. J. (2011). Genetics and pathogenesis of inflammatory bowel disease. Nature, 474(7351), 307–317. https://doi.org/10.1038/nature10209
Kolls, J. K., & Lindén, A. (2004). Interleukin-17 family members and inflammation. Immunity, 21(4), 467–476. https://doi.org/10.1016/j.immuni.2004.08.018
Koukos, G., Polytarchou, C., Kaplan, J. L., Morley-Fletcher, A., Gras-Miralles, B., Kokkotou, E., ... & Pothoulakis, C. (2013). MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis. Gastroenterology, 145(4), 842–852. https://doi.org/10.1053/j.gastro.2013.07.001
Krützfeldt, J., Rajewsky, N., Braich, R., Rajeev, K. G., Tuschl, T., Manoharan, M., & Stoffel, M. (2005). Silencing of microRNAs in vivo with 'antagomirs'. Nature, 438(7068), 685–689. https://doi.org/10.1038/nature04303
Lamprecht, A., Ubrich, N., Yamamoto, H., Schäfer, U., Takeuchi, H., Lehr, C. M., ... & Maincent, P. (2005). Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease. Journal of Pharmacology and Experimental Therapeutics, 299(2), 775–781. https://doi.org/10.1016/S0022-3565(24)29290-9
Lee, J. S., Tato, C. M., Joyce-Shaikh, B., Gulen, M. F., Gulan, F., Cayatte, C., ... & Cua, D. J. (2015). Interleukin-23-independent IL-17 production regulates intestinal epithelial permeability. Immunity, 43(4), 727–738. https://doi.org/10.1016/j.immuni.2015.09.003
Ley, K., Laudanna, C., Cybulsky, M. I., & Nourshargh, S. (2007). Getting to the site of inflammation: The leukocyte adhesion cascade updated. Nature Reviews Immunology, 7(9), 678–689. https://doi.org/10.1038/nri2156
Li, M. O., & Flavell, R. A. (2008). TGF-β: A master of all T cell trades. Cell, 134(3), 392–404. https://doi.org/10.1016/j.cell.2008.07.025
Li, M. O., Wan, Y. Y., Sanjabi, S., Robertson, A. K. L., & Flavell, R. A. (2006). Transforming growth factor-β regulation of immune responses. Annual Review of Immunology, 24, 99–146. https://doi.org/10.1146/annurev.immunol.24.021605.090737
Maul, J., Loddenkemper, C., Mundt, P., Berg, E., Giese, T., Stallmach, A., ... & Zeitz, M. (2005). Peripheral and intestinal regulatory CD4?CD25high T cells in inflammatory bowel disease. Gastroenterology, 128(7), 1868–1878. https://doi.org/10.1053/j.gastro.2005.03.043
Meylan, F., Davidson, T. S., Kahle, E., Kinder, M., Acharya, K., Jankovic, D., ... & Siegel, R. M. (2008). The TNF-family receptor DR3 is essential for diverse T cell–mediated inflammatory diseases. Immunity, 29(1), 79–89. https://doi.org/10.1016/j.immuni.2008.04.021
Monteleone, G., Kumberova, A., Croft, N. M., McKenzie, C., Steer, H. W., & MacDonald, T. T. (2001). Blocking Smad7 restores TGF-β1 signaling in chronic inflammatory bowel disease. Journal of Clinical Investigation, 108(4), 601–609. https://doi.org/10.1172/JCI12821
Monteleone, G., Neurath, M. F., Ardizzone, S., Di Sabatino, A., Fantini, M. C., Castiglione, F., ... & Colombel, J. F. (2015). Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease. New England Journal of Medicine, 372(12), 1104–1113. https://doi.org/10.1056/NEJMoa1407250
Monteleone, G., Pallone, F., & MacDonald, T. T. (2012). Smad7 in TGF-β signaling. Cell Research, 22(1), 21–22.
Neurath, M. F. (2007). IL-23: A master regulator in Crohn disease. Nature Medicine, 13(1), 26–28. https://doi.org/10.1038/nm0107-26
Neurath, M. F. (2017). Current and emerging therapeutic targets for IBD. Nature Reviews Gastroenterology & Hepatology, 14(3), 269–278. https://doi.org/10.1038/nrgastro.2016.208
Ng, S. C., Shi, H. Y., Hamidi, N., Underwood, F. E., Tang, W., Benchimol, E. I., ... & Kaplan, G. G. (2017). Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies. Lancet, 390(10114), 2769–2778. https://doi.org/10.1016/S0140-6736(17)32448-0
Oppmann, B., Lesley, R., Blom, B., Timans, J. C., Xu, Y., Hunte, B., ... & Kastelein, R. A. (2000). Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity, 13(5), 715–725. https://doi.org/10.1016/S1074-7613(00)00070-4
O’Shea, J. J., Schwartz, D. M., Villarino, A. V., Gadina, M., McInnes, I. B., & Laurence, A. (2015). The JAK–STAT pathway: Impact on human disease and therapeutic intervention. Annual Review of Medicine, 66, 311–328. https://doi.org/10.1146/annurev-med-051113-024537
Paramsothy, S., Kamm, M. A., Kaakoush, N. O., Walsh, A. J., van den Bogaerde, J., Samuel, D., ... & Borody, T. J. (2017). Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: A randomised placebo-controlled trial. Lancet, 389(10075), 1218–1228. https://doi.org/10.1016/S0140-6736(17)30182-4
Peters, L. A., Perrigoue, J., Mortha, A., Iuga, A., Song, W. M., Neiman, E. M., ... & Friedman, J. R. (2017). A functional genomics predictive network model identifies regulators of inflammatory bowel disease. Nature Genetics, 49(10), 1437–1449. https://doi.org/10.1038/ng.3947
Peterson, L. W., & Artis, D. (2014). Intestinal epithelial cells: Regulators of barrier function and immune homeostasis. Nature Reviews Immunology, 14(3), 141–153. https://doi.org/10.1038/nri3608
Peyrin-Biroulet, L., Sandborn, W., Sands, B. E., Reinisch, W., Bemelman, W., Bryant, R. V., ... & van Assche, G. (2015). Selecting therapeutic targets in inflammatory bowel disease (STRIDE): Determining therapeutic goals for treat-to-target. American Journal of Gastroenterology, 110(9), 1324–1338. https://doi.org/10.1038/ajg.2015.233
https://doi.org/10.1038/ajg.2015.233
Rieder, F., & Fiocchi, C. (2009). Intestinal fibrosis in IBD—a dynamic, multifactorial process. Nature Reviews Gastroenterology & Hepatology, 6(4), 228–235. https://doi.org/10.1038/nrgastro.2009.31
Rioux, J. D., Xavier, R. J., Taylor, K. D., Silverberg, M. S., Goyette, P., Huett, A., ... & Daly, M. J. (2007). Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nature Genetics, 39(5), 596–604. https://doi.org/10.1038/ng2032
Roth, L., MacDonald, J. K., McDonald, J. W., & Chande, N. (2016). Systematic review: The effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in patients with an inadequate response to methotrexate. Cochrane Database of Systematic Reviews, 4, CD010893.
Rupaimoole, R., & Slack, F. J. (2017). MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nature Reviews Drug Discovery, 16(3), 203–222. https://doi.org/10.1038/nrd.2016.246
Sandborn, W. J., Gasink, C., Gao, L. L., Blank, M. A., Johanns, J., Guzzo, C., ... & Hanauer, S. B. (2012). Ustekinumab induction and maintenance therapy in refractory Crohn's disease. New England Journal of Medicine, 367(16), 1519–1528. https://doi.org/10.1056/NEJMoa1203572
Sandborn, W. J., Ghosh, S., Panes, J., Vranic, I., Su, C., Rousell, S., & Niezychowski, W. (2017). Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. New England Journal of Medicine, 376(18), 1723–1736. https://doi.org/10.1056/NEJMoa1606910
Sandborn, W. J., Colombel, J. F., Sands, B. E., Rutgeerts, P., Targan, S. R., Panaccione, R., ... & Loftus, E. V. Jr. (2019). Abatacept for Crohn's disease and ulcerative colitis. Gastroenterology, 156(4), 946–957.
Sands, B. E., Chen, J., Feagan, B. G., Penney, M., Rees, W. A., Danese, S., ... & Jacobstein, D. (2017). Efficacy and safety of MEDI2070, an antibody against interleukin 23, in patients with moderate to severe Crohn's disease: A phase 2a study. Gastroenterology, 153(1), 77–86. https://doi.org/10.1053/j.gastro.2017.03.049
Sartor, R. B., & Wu, G. D. (2017). Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches. Gastroenterology, 152(2), 327–339. https://doi.org/10.1053/j.gastro.2016.10.012
Schoepfer, A. M., Beglinger, C., Straumann, A., Trummler, M., Vavricka, S. R., Bruegger, L. E., & Seibold, F. (2010). Fecal calprotectin correlates more closely with the Simple Endoscopic Score for Crohn's disease (SES-CD) than CRP, blood leukocytes, and the CDAI. American Journal of Gastroenterology, 105(1), 162–169. https://doi.org/10.1038/ajg.2009.545
Schwartz, D. M., Bonelli, M., Gadina, M., & O'Shea, J. J. (2016). Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nature Reviews Rheumatology, 12(1), 25–36. https://doi.org/10.1038/nrrheum.2015.167
Sharma, A., Rudra, D., Bansal, R., Suresh, R., Kim, S. W., & Naga Prasad, S. V. (2015). Role of miRNA in modulating immune responses in atopic dermatitis and asthma. Protein & Cell, 6(12), 847–862.
Soler, D., Chapman, T., Yang, L. L., Wyant, T., Egan, R., & Fedyk, E. R. (2009). The binding specificity and selective antagonism of vedolizumab, an anti-α4β7 integrin therapeutic antibody in development for inflammatory bowel diseases. Journal of Pharmacology and Experimental Therapeutics, 330(3), 864–875. https://doi.org/10.1124/jpet.109.153973
Sonnenberg, G. F., Fouser, L. A., & Artis, D. (2011). Border patrol: Regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nature Immunology, 12(5), 383–390. https://doi.org/10.1038/ni.2025
Speca, S., Giusti, I., Rieder, F., & Latella, G. (2012). Cellular and molecular mechanisms of intestinal fibrosis. World Journal of Gastroenterology, 18(28), 3635–3661. https://doi.org/10.3748/wjg.v18.i28.3635
Steeland, S., Libert, C., & Vandenbroucke, R. E. (2018). A new venue of TNF targeting. International Journal of Molecular Sciences, 19(5), 1442. https://doi.org/10.3390/ijms19051442
Strober, W., & Fuss, I. J. (2011). Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology, 140(6), 1756–1767. https://doi.org/10.1053/j.gastro.2011.02.016
Takedatsu, H., Michelsen, K. S., Wei, B., Landers, C. J., Thomas, L. S., Dhall, D., ... & Targan, S. R. (2008). TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. Gastroenterology, 135(2), 552–567. https://doi.org/10.1053/j.gastro.2008.04.037
Torres, J., Mehandru, S., Colombel, J. F., & Peyrin-Biroulet, L. (2017). Crohn's disease. Lancet, 389(10080), 1741–1755. https://doi.org/10.1016/S0140-6736(16)31711-1
Tracey, D., Klareskog, L., Sasso, E. H., Salfeld, J. G., & Tak, P. P. (2008). Tumor necrosis factor antagonist mechanisms of action: A comprehensive review. Pharmacology & Therapeutics, 117(2), 244–279. https://doi.org/10.1016/j.pharmthera.2007.10.001
Vermeire, S., Noman, M., Van Assche, G., Baert, F., D'Haens, G., & Rutgeerts, P. (2007). Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn's disease. Gut, 56(9), 1226–1231. https://doi.org/10.1136/gut.2006.099978
Villarino, A. V., Kanno, Y., & O'Shea, J. J. (2017). Mechanisms and consequences of Jak-STAT signaling in the immune system. Nature Immunology, 18(4), 374–384. https://doi.org/10.1038/ni.3691
Vong, L. B., & Nagasaki, Y. (2016). Combination treatment of murine colon cancer with doxorubicin and redox nanoparticles. Molecular Pharmaceutics, 13(2), 449–455. https://doi.org/10.1021/acs.molpharmaceut.5b00676
Vong, L. B., Tomita, T., Yoshitomi, T., Matsui, H., & Nagasaki, Y. (2012). An orally administered redox nanoparticle that accumulates in the colonic mucosa and reduces colitis in mice. Gastroenterology, 143(4), 1027–1036. https://doi.org/10.1053/j.gastro.2012.06.043
Wajant, H., Pfizenmaier, K., & Scheurich, P. (2003). Tumor necrosis factor signaling. Cell Death & Differentiation, 10(1), 45–65. https://doi.org/10.1038/sj.cdd.4401189
Winthrop, K. L. (2017). The emerging safety profile of JAK inhibitors in rheumatic disease. Nature Reviews Rheumatology, 13(4), 234–243. https://doi.org/10.1038/nrrheum.2017.23
Wu, F., Zikusoka, M., Trindade, A., Dassopoulos, T., Harris, M. L., Bayless, T. M., ... & Kwon, J. H. (2008). MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2α. Gastroenterology, 135(5), 1624–1635. https://doi.org/10.1053/j.gastro.2008.07.068
Yang, S. K., Hong, M., Baek, J., Choi, H., Zhao, W., Jung, Y., ... & Song, K. (2008). A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nature Genetics, 46(9), 1017–1020. https://doi.org/10.1038/ng.3060
Yu, Q. T., Saruta, M., Avanesyan, A., Fleshner, P. R., Banham, A. H., & Papadakis, K. A. (2007). Expression and functional characterization of FOXP3+ CD4+ regulatory T cells in ulcerative colitis. Inflammatory Bowel Diseases, 13(2), 191–199. https://doi.org/10.1002/ibd.20053
Zundler, S., & Neurath, M. F. (2015). Interleukin-12: Functional activities and implications for disease. Cytokine & Growth Factor Reviews, 26(5), 559–568. https://doi.org/10.1016/j.cytogfr.2015.07.003
Zundler, S., Becker, E., Spocinska, M., Slawik, M., Parga-Vidal, L., Stark, R., ... & Neurath, M. F. (2019). Hobit- and Blimp-1-driven CD4+ tissue-resident memory T cells control chronic intestinal inflammation. Nature Immunology, 20(3), 288–300. https://doi.org/10.1038/s41590-018-0298-