The ubiquitous role of spleen tyrosine kinase (Syk) in gut diseases: From mucosal immunity to targeted therapy

References

• Geahlen RL. Getting Syk: spleen tyrosine kinase as a therapeutic target. Trends Pharmacol Sci. 2014;35(8):414–422. doi:10.1016/j.tips.2014.05.007.
   PubMed Web of Science ®Google Scholar
• Szilveszter KP, Németh T, Mócsai A. Tyrosine kinases in autoimmune and inflammatory skin diseases. Front Immunol. 2019;10:1862. doi:10.3389/fimmu.2019.01862.
   PubMed Web of Science ®Google Scholar
• Alhazmi A. Spleen tyrosine kinase as a target therapy for pseudomonas aeruginosa infection. J Innate Immun. 2018;10(4):255–263. doi:10.1159/000489863.
   PubMed Web of Science ®Google Scholar
• Abtahian F, Guerriero A, Sebzda E, et al. Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science. 2003;299(5604):247–251. doi:10.1126/science.1079477.
   PubMed Web of Science ®Google Scholar
• Ma TK, McAdoo SP, Tam FW. Spleen tyrosine kinase: a crucial player and potential therapeutic target in renal disease. Nephron. 2016;133(4):261–269. doi:10.1159/000446879.
   PubMed Web of Science ®Google Scholar
• Mócsai A, Ruland J, Tybulewicz VL. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol. 2010;10(6):387–402. doi:10.1038/nri2765.
   PubMed Web of Science ®Google Scholar
• Kulathu Y, Grothe G, Reth M. Autoinhibition and adapter function of Syk. Immunol Rev. 2009;232(1):286–299. doi:10.1111/j.1600-065X.2009.00837.x.
   PubMedGoogle Scholar
• Zhang K, Hornef MW, Dupont A. The intestinal epithelium as guardian of gut barrier integrity. Cell Microbiol. 2015;17(11):1561–1569. doi:10.1111/cmi.12501.
   PubMed Web of Science ®Google Scholar
• Lee YM, Ayres JS. Decoding the intestinal epithelium cell by cell. Nat Immunol. 2018;19(1):7–9. doi:10.1038/s41590-017-0011-0.
   PubMed Web of Science ®Google Scholar
• Allaire JM, Crowley SM, Law HT, et al. The intestinal epithelium: central coordinator of mucosal immunity. Trends Immunol. 2018;39(9):677–696. doi:10.1016/j.it.2018.04.002.
   PubMed Web of Science ®Google Scholar
• Nadatani Y, Watanabe T, Shimada S, et al. Microbiome and intestinal ischemia/reperfusion injury. J Clin Biochem Nutr. 2018;63(1):26–32. doi:10.3164/jcbn.17-137.
   PubMed Web of Science ®Google Scholar
• Zou L, Sato N, Kone BC. Alpha-melanocyte stimulating hormone protects against H2O2-induced inhibition of wound restitution in IEC-6 cells via a Syk kinase- and NF-kappabeta-dependent mechanism. Shock. 2004;22:453–459.
   PubMed Web of Science ®Google Scholar
• Wheeler ML, Limon JJ, Bar AS, et al. Immunological consequences of intestinal fungal dysbiosis. Cell Host Microbe. 2016;19(6):865–873. doi:10.1016/j.chom.2016.05.003.
   PubMed Web of Science ®Google Scholar
• Goyal S, Castrillón-Betancur JC, Klaile E, Slevogt H. The interaction of human pathogenic fungi with C-type lectin receptors. Front Immunol. 2018;9:1261. doi:10.3389/fimmu.2018.01261.
   PubMed Web of Science ®Google Scholar
• Iliev ID, Funari VA, Taylor KD, et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science. 2012;336(6086):1314–1317. doi:10.1126/science.1221789.
   PubMed Web of Science ®Google Scholar
• Cohen-Kedar S, Baram L, Elad H, et al. Human intestinal epithelial cells respond to β-glucans via Dectin-1 and Syk. Eur J Immunol. 2014;44(12):3729–3740. doi:10.1002/eji.201444876.
   PubMed Web of Science ®Google Scholar
• Sancho D, Reis e Sousa C. Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu Rev Immunol. 2012;30:491–529. doi:10.1146/annurev-immunol-031210-101352.
   PubMed Web of Science ®Google Scholar
• Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med. 2016;375(24):2369–2379. doi:10.1056/NEJMra1600266.
   PubMed Web of Science ®Google Scholar
• Murata Y, Kotani T, Supriatna Y, et al. Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium. Proc Natl Acad Sci U S A. 2015;112(31):E4264–4271. doi:10.1073/pnas.1510167112.
   PubMed Web of Science ®Google Scholar
• Mori S, Kamei N, Murata Y, et al. Microvillus-specific protein tyrosine phosphatase SAP-1 plays a role in regulating the intestinal paracellular transport of macromolecules. J Pharm Sci. 2017;106(9):2904–2908. doi:10.1016/j.xphs.2017.04.014.
   PubMed Web of Science ®Google Scholar
• Van Hung T, Suzuki T. Guar gum fiber increases suppressor of cytokine signaling-1 expression via toll-like receptor 2 and dectin-1 pathways, regulating inflammatory response in small intestinal epithelial cells. Mol Nutr Food Res. 2017;61:1700048. doi:10.1002/mnfr.201700048.
   Web of Science ®Google Scholar
• Hung TV, Suzuki T. Short-chain fatty acids suppress inflammatory reactions in Caco-2 cells and mouse colons. J Agric Food Chem. 2018;66(1):108–117. doi:10.1021/acs.jafc.7b04233.
   PubMed Web of Science ®Google Scholar
• Dasgupta N, Thakur BK, Ta A, Dutta P, Das S. Suppression of spleen tyrosine kinase (Syk) by histone deacetylation promotes, whereas BAY61-3606, a synthetic syk inhibitor abrogates colonocyte apoptosis by ERK activation. J Cell Biochem. 2017;118(1):191–203. doi:10.1002/jcb.25625.
   PubMed Web of Science ®Google Scholar
• Bain CC, Schridde A. Origin, differentiation, and function of intestinal macrophages. Front Immunol. 2018;9:2733. doi:10.3389/fimmu.2018.02733.
   PubMed Web of Science ®Google Scholar
• Charles JF, Humphrey MB, Zhao X, et al. The innate immune response to Salmonella enterica serovar Typhimurium by macrophages is dependent on TREM2-DAP12. Infect Immun. 2008;76(6):2439–2447. doi:10.1128/IAI.00115-08.
   PubMed Web of Science ®Google Scholar
• Dharmaraja AT. Role of reactive oxygen species (ROS) in therapeutics and drug resistance in cancer and bacteria. J Med Chem. 2017;60(8):3221–3240. doi:10.1021/acs.jmedchem.6b01243.
   PubMed Web of Science ®Google Scholar
• Wu S-Y, Huang J-H, Chen W-Y, et al. Cell intrinsic galectin-3 attenuates neutrophil ROS-dependent killing of Candida by modulating CR3 downstream Syk activation. Front Immunol. 2017;8:48. doi:10.3389/fimmu.2017.00048.
   PubMed Web of Science ®Google Scholar
• Lima-Junior DS, Mineo TWP, Calich VLG, Zamboni DS. Dectin-1 activation during leishmania amazonensis phagocytosis prompts Syk-dependent reactive oxygen species production to trigger inflammasome assembly and restriction of parasite replication. J Immunol. 2017;199(6):2055–2068. doi:10.4049/jimmunol.1700258.
   PubMed Web of Science ®Google Scholar
• Biagioli M, Mencarelli A, Carino A, et al. Genetic and pharmacological dissection of the role of spleen tyrosine kinase (Syk) in intestinal inflammation and immune dysfunction in inflammatory bowel diseases. Inflamm Bowel Dis. 2017;24(1):123–135. doi:10.1093/ibd/izx031.
   PubMed Web of Science ®Google Scholar
• Gong W, Guo K, Zheng T, et al. Preliminary exploration of the potential of spliceosome-associated protein 130 for predicting disease severity in Crohn’s disease. Ann NY Acad Sci. 2020;1462(1):128–138. doi:10.1111/nyas.14240.
   PubMed Web of Science ®Google Scholar
• Gong W, et al. Mincle/Syk signaling promotes intestinal mucosal inflammation through induction of macrophage pyroptosis in Crohn’s disease. J Crohns Colitis. 2020;14:1734–1747. doi:10.1093/ecco-jcc/jjaa088.
   PubMed Web of Science ®Google Scholar
• Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 2011;11(11):762–774. doi:10.1038/nri3070.
   PubMed Web of Science ®Google Scholar
• Kennedy JJ, Steain M, Slobedman B, Abendroth A. Infection and functional modulation of human monocytes and macrophages by varicella-zoster virus. J Virol. 2019;93. doi:10.1128/JVI.01887-18.
   Web of Science ®Google Scholar
• Guilliams M, Mildner A, Yona S. Developmental and functional heterogeneity of monocytes. Immunity. 2018;49(4):595–613. doi:10.1016/j.immuni.2018.10.005.
   PubMed Web of Science ®Google Scholar
• Shibuya A, Nakahashi-Oda C, Tahara-Hanaoka S. Regulation of immune responses by the activating and inhibitory myeloid-associate immunoglobuline-like receptors (MAIR) (CD300). Immune Netw. 2009;9(2):41–45. doi:10.4110/in.2009.9.2.41.
   PubMedGoogle Scholar
• Totsuka N, Kim Y-G, Kanemaru K, et al. Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration. Nat Commun. 2014;5:4710. doi:10.1038/ncomms5710.
   PubMed Web of Science ®Google Scholar
• Zucchetto A, Tissino E, Chigaev A, Hartmann TN, Gattei V. Methods for investigating VLA-4 (CD49d/CD29) expression and activation in chronic lymphocytic leukemia and its clinical applications. Methods Mol Biol. 2019;1881:101–112. doi:10.1007/978-1-4939-8876-1_8.
   PubMedGoogle Scholar
• Tissino E, Benedetti D, Herman SEM, et al. Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia. J Exp Med. 2018;215(2):681–697. doi:10.1084/jem.20171288.
   PubMed Web of Science ®Google Scholar
• Leonardi I, Li X, Semon A, et al. CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi. Science. 2018;359(6372):232–236. doi:10.1126/science.aao1503.
   PubMed Web of Science ®Google Scholar
• Li X, Leonardi I, Semon A, et al. Response to fungal dysbiosis by gut-resident CX3CR1+ mononuclear phagocytes aggravates allergic airway disease. Cell Host Microbe. 2018;24(6):847–856.e4. doi:10.1016/j.chom.2018.11.003.
   PubMed Web of Science ®Google Scholar
• Malik A, Sharma D, Malireddi RKS, et al. SYK-CARD9 signaling axis promotes gut fungi-mediated inflammasome activation to restrict colitis and colon cancer. Immunity. 2018;49(3):515–530.e5. doi:10.1016/j.immuni.2018.08.024.
   PubMed Web of Science ®Google Scholar
• Worbs T, Hammerschmidt SI, Förster R. Dendritic cell migration in health and disease. Nat Rev Immunol. 2017;17(1):30–48. doi:10.1038/nri.2016.116.
   PubMed Web of Science ®Google Scholar
• Weiss G, Maaetoft-Udsen K, Stifter SA, et al. MyD88 drives the IFN-β response to Lactobacillus acidophilus in dendritic cells through a mechanism involving IRF1, IRF3, and IRF7. J Immunol. 2012;189(6):2860–2868. doi:10.4049/jimmunol.1103491.
   PubMed Web of Science ®Google Scholar
• Blum AM, Hang L, Setiawan T, et al. Heligmosomoides polygyrus bakeri induces tolerogenic dendritic cells that block colitis and prevent antigen-specific gut T cell responses. J Immunol. 2012;189(5):2512–2520. doi:10.4049/jimmunol.1102892.
   PubMed Web of Science ®Google Scholar
• Hang L, Blum AM, Kumar S, et al. Downregulation of the Syk signaling pathway in intestinal dendritic cells is sufficient to induce dendritic cells that inhibit colitis. J Immunol. 2016;197(7):2948–2957. doi:10.4049/jimmunol.1600063.
   PubMed Web of Science ®Google Scholar
• Lamprinaki D, Beasy G, Zhekova A, et al. LC3-associated phagocytosis is required for dendritic cell inflammatory cytokine response to gut commensal yeast Saccharomyces cerevisiae. Front Immunol. 2017;8:1397. doi:10.3389/fimmu.2017.01397.
   PubMed Web of Science ®Google Scholar
• Bekiaris V, Persson EK, Agace WW. Intestinal dendritic cells in the regulation of mucosal immunity. Immunol Rev. 2014;260(1):86–101. doi:10.1111/imr.12194.
   PubMed Web of Science ®Google Scholar
• Muzaki ARBM, Tetlak P, Sheng J, et al. Intestinal CD103(+)CD11b(-) dendritic cells restrain colitis via IFN-γ-induced anti-inflammatory response in epithelial cells. Mucosal Immunol. 2016;9(2):336–351. doi:10.1038/mi.2015.64.
   PubMed Web of Science ®Google Scholar
• Hansen IS, Krabbendam L, Bernink JH, et al. FcαRI co-stimulation converts human intestinal CD103+ dendritic cells into pro-inflammatory cells through glycolytic reprogramming. Nat Commun. 2018;9(1):863. doi:10.1038/s41467-018-03318-5.
   PubMedGoogle Scholar
• Bernink JH, Krabbendam L, Germar K, et al. Interleukin-12 and -23 control plasticity of CD127(+) Group 1 and Group 3 innate lymphoid cells in the intestinal lamina propria. Immunity. 2015;43(1):146–160. doi:10.1016/j.immuni.2015.06.019.
   PubMed Web of Science ®Google Scholar
• Joeris T, Muller-Luda K, Agace WW, Mowat AM. Diversity and functions of intestinal mononuclear phagocytes. Mucosal Immunol. 2017;10(4):845–864. doi:10.1038/mi.2017.22.
   PubMed Web of Science ®Google Scholar
• Dzharullaeva AS, et al. Stimulation of dectin-1 and dectin-2 during parenteral immunization, but not mincle, induces secretory iga in intestinal mucosa. J Immunol Res. 2018;3835720.
   Google Scholar
• Hirota K, Turner J-E, Villa M, et al. Plasticity of Th17 cells in Peyer’s patches is responsible for the induction of T cell-dependent IgA responses. Nat Immunol. 2013;14(4):372–379. doi:10.1038/ni.2552.
   PubMed Web of Science ®Google Scholar
• Bäumler AJ, Sperandio V. Interactions between the microbiota and pathogenic bacteria in the gut. Nature. 2016;535(7610):85–93. doi:10.1038/nature18849.
   PubMed Web of Science ®Google Scholar
• Honda K, Littman DR. The microbiota in adaptive immune homeostasis and disease. Nature. 2016;535(7610):75–84. doi:10.1038/nature18848.
   PubMed Web of Science ®Google Scholar
• Martínez-López M, Iborra S, Conde-Garrosa R, et al. Microbiota sensing by Mincle-Syk axis in dendritic cells regulates interleukin-17 and -22 production and promotes intestinal barrier integrity. Immunity. 2019;50(2):446–461. doi:10.1016/j.immuni.2018.12.020.
   PubMed Web of Science ®Google Scholar
• Siebenhaar F, Redegeld FA, Bischoff SC, Gibbs BF, Maurer M. Mast cells as drivers of disease and therapeutic targets. Trends Immunol. 2018;39(2):151–162. doi:10.1016/j.it.2017.10.005.
   PubMed Web of Science ®Google Scholar
• Albert-Bayo M, et al. Intestinal mucosal mast cells: key modulators of barrier function and homeostasis. Cells. 2019;8:E135. doi:10.3390/cells8020135.
   PubMed Web of Science ®Google Scholar
• Wouters MM, Vicario M, Santos J. The role of mast cells in functional GI disorders. Gut. 2016;65(1):155–168. doi:10.1136/gutjnl-2015-309151.
   PubMed Web of Science ®Google Scholar
• Enck P, Aziz Q, Barbara G, et al. Irritable bowel syndrome. Nat Rev Dis Primers. 2016;2:16014. doi:10.1038/nrdp.2016.14.
   PubMed Web of Science ®Google Scholar
• Botschuijver S, Roeselers G, Levin E, et al. Intestinal fungal dysbiosis is associated with visceral hypersensitivity in patients with irritable bowel syndrome and rats. Gastroenterology. 2017;153(4):1026–1039. doi:10.1053/j.gastro.2017.06.004.
   PubMed Web of Science ®Google Scholar
• Braak B, Klooker TK, Wouters MM, et al. Mucosal immune cell numbers and visceral sensitivity in patients with irritable bowel syndrome: is there any relationship?Am J Gastroenterol. 2012;107(5):715–726. doi:10.1038/ajg.2012.54.
   PubMed Web of Science ®Google Scholar
• Lucas MC, Goldstein DM, Hermann JC, et al. Rational design of highly selective spleen tyrosine kinase inhibitors. J Med Chem. 2012;55(23):10414–10423. doi:10.1021/jm301367c.
   PubMed Web of Science ®Google Scholar
• Ellis JM, Altman MD, Bass A, et al. Overcoming mutagenicity and ion channel activity: optimization of selective spleen tyrosine kinase inhibitors. J Med Chem. 2015;58(4):1929–1939. doi:10.1021/jm5018169.
   PubMed Web of Science ®Google Scholar
• Kurniawan DW, Storm G, Prakash J, Bansal R. Role of spleen tyrosine kinase in liver diseases. World J Gastroenterol. 2020;26(10):1005–1019. doi:10.3748/wjg.v26.i10.1005.
   PubMed Web of Science ®Google Scholar
• Pamuk ON, Lapchak PH, Rani P, et al. Spleen tyrosine kinase inhibition prevents tissue damage after ischemia-reperfusion. Am J Physiol Gastrointest Liver Physiol. 2010;299(2):G391–G399. doi:10.1152/ajpgi.00198.2010.
   PubMed Web of Science ®Google Scholar
• Gong W, Yu J, Zheng T, et al. CCL4-mediated targeting of spleen tyrosine kinase (Syk) inhibitor using nanoparticles alleviates inflammatory bowel disease. Clin Transl Med. 2021;11(2):e339. doi:10.1002/ctm2.339.
   PubMed Web of Science ®Google Scholar
• Can G, Ayvaz S, Can H, et al. The Syk inhibitor fostamatinib decreases the severity of colonic mucosal damage in a rodent model of colitis. J Crohns Colitis. 2015;9(10):907–917. doi:10.1093/ecco-jcc/jjv114.
   PubMed Web of Science ®Google Scholar
• Biancheri P, Foster MR, Fyfe MCT, et al. Effect of narrow spectrum versus selective kinase inhibitors on the intestinal proinflammatory immune response in ulcerative colitis. Inflamm Bowel Dis. 2016;22(6):1306–1315. doi:10.1097/MIB.0000000000000759.
   PubMed Web of Science ®Google Scholar
• Bloemendaal FM, Koelink PJ, van Schie KA, et al. TNF-anti-TNF immune complexes inhibit IL-12/IL-23 secretion by inflammatory macrophages via an Fc-dependent mechanism. J Crohns Colitis. 2018;12(9):1122–1130. doi:10.1093/ecco-jcc/jjy075.
   PubMed Web of Science ®Google Scholar
• van Bree SHW, Gomez-Pinilla PJ, van de Bovenkamp FS, et al. Inhibition of spleen tyrosine kinase as treatment of postoperative ileus. Gut. 2013;62(11):1581–1590. doi:10.1136/gutjnl-2012-302615.
   PubMed Web of Science ®Google Scholar