In the words of Hippocrates, all disease begin in the gut. In the intestinal lumen, there are more than 1000 species of microbiota members containing 600,000 genes. that is 10 times more than the number of nucleated cells in our body. Connections such as tight junction (TJ) and adherens junction (AJ) between epithelial cells prevent the passage of microorganisms and antigens to the lamina proprea, while transmitting the received stimuli with signaling mechanisms. Integrin and immunoglobulin like adhesion molecules, which are members of the tight junction, receive signaling with ErbB (Her1, EGFR/2/3) and cytokine receptors (transforming growth factor TGFβ receptors) and transmit them to the nucleus, creating signals for gene transcription, proliferation, differentiation, cytokine synthesis, synthesis of surface receptors, epithelial mesenchimal transition (Emt) regulation, or apoptosis and growth arrest. Tight junction transmembrane proteins, scaffolding proteins such as zonulin, communicate with afadin-mediated AJ, allowing signals to be transmitted to the cytoskeleton. It makes gene expression with the transcription factor to which it is attached. It contributes to the ion balance with claudin, cytoskeleton regulation with occludin, gene transcription and cytokine synthesis with Marveld3, from the members of the TAMPs family to which it is linked. The stimulated cell synthesizes Wingless-ınt1 (Wnt) signaling molecules and performs paracrine and autocrine signaling. It balances intracellular Ca+2 level with non-canonical Wnt pathway, provides cell polarity especially via Cell division control protein 42 (CDC42) with non-canonical polarity pathway, β-catenin mediated gene transcription with canonical Wnt pathway. While microbial antigens are recognized by Toll like receptors (TLR) and cytokines are synthesized, antigen molecule presentation is regulated by major histocompatibility complex (Mhc) molecules. Cytokines synthesized by signaling trigger innate immunity in the lamina propria (LP) and adaptive immunity consisting of 50x109 lymphocytis, thereby initiating the anti-inflammatory or pro-inflammatory process. This review describes all these mechanisms and their connections.
| Published in | Cell Biology (Volume 10, Issue 2) |
| DOI | 10.11648/j.cb.20221002.11 |
| Page(s) | 41-52 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
Tight Junction, Zonulin, CDC42, Gut Homing, B1 Lymphocytes
| [1] | Abbas A. K, Lichtman A. H, Pillai S. (2018), Cellular and Molecular Immunology (9th ed), Philadelphia, PA: Elsevier. |
| [2] | Steinbacher T., Kummer D., Ebnet K. Junctional adhesion molecule-A: functional diversity through molecular promiscuity. Cell Mol Life Sci 2018; 75: 1393–1409. |
| [3] | Peddibhotlaa S. S. D., Brinkmanna B. F. Tetraspanin CD9 links junctional adhesion molecule-A to αvβ3 integrin to mediate basic fibroblast growth factor specific angiogenic signaling. Mol Biol Cell. 2013; 24 (7): 933–944. |
| [4] | Reyes R., Cardeñes B., Machado-Pineda Y., Cabañas C. Tetraspanin CD9: A Key Regulator of Cell Adhesion in the Immune System. Front Immunol 2018; 30; 9: 863. |
| [5] | Gutie´rrez-Lo´pez M., Gilsanz A., Ya´n˜ez-Mo´ M. et al. The sheddase activity of ADAM17/TACE is regulated by the tetraspanin CD9. Cell. Mol. Life Sci. (2011) 68: 3275–3292. |
| [6] | Zhao X., Guan J., Focal adhesion kinase and its signaling pathways in cell migration and angiogenesis. Adv Drug Deliv Rev. 2011; 63 (8): 610-5. |
| [7] | Oldham W. M., Hamm H. E. Heterotrimeric G protein activation by G-protein-coupled receptors. Nat Rev. Mol Cell Biol2008; 9, 60–71. |
| [8] | Kawasakı h., sprıngett g. m., mochızukı n., A family of cAMP-binding proteins that directly activate Rap1. SCIENCE 1998; 282, 5397, 2275-2279. |
| [9] | Kosuru R., Chrzanowska M. integration of rap1 and calcium signaling. Int J Mol Sci. 2020; 21 (5): 1616. |
| [10] | Monteiro A. C., Sumagin R., Rankin C. R., ET AL. JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function. Mol Biol Cell. 2013 Sep 15; 24 (18): 2849–2860. |
| [11] | Lu S., Jang H., Muratcioglu S. ET AL. Ras Conformational Ensembles, Allostery, and Signaling. Chem Rev 2016; 116 (11): 6607-65. |
| [12] | Sami A., Karsy M. Targeting the PI3K/AKT/mTOR signaling pathway in glioblastoma: novel therapeutic agents and advances in understanding. Tumour Biol. 2013; 34 (4): 1991-2002. |
| [13] | Sundqvist A., Vasilaki E., Voytyuk O., ET AL. TGFβ and EGF signaling orchestrates the AP-1- and p63 transcriptional regulation of breast cancer invasiveness. Oncogene; (2020) 39, 4436–4449. |
| [14] | Oltmanns U., Issa R., Sukkar M. B. Role of c-jun N-terminal kinase in the induced release of GM-CSF, RANTES and IL-8 from human airway smooth muscle cells. Br J Pharmacol. 2003 Jul; 139 (6): 1228–1234. |
| [15] | Olson C., Hedrick M. N., Izadi H. p38 Mitogen-Activated Protein Kinase Controls NF-κB Transcriptional Activation and Tumor Necrosis Factor Alpha Production through RelA Phosphorylation Mediated by Mitogen- and Stress-Activated Protein Kinase 1 in Response to Borrelia burgdorferi Antigens. Infect Immun. 2007; 75 (1): 270-7. |
| [16] | Moya I. V., HaldeR G. Hippo–YAP/TAZ signalling in organ regeneration and regenerative medicine. Nat Rev Mol Cell Biol. 2019; 20 (4): 211-226. |
| [17] | Chen X, Li Y, Luo J, Hou N. Molecular Mechanism of Hippo–YAP1/TAZ Pathway in Heart Development, Disease, and Regeneration. Front Physiol. 2020; 11: 389. |
| [18] | Garcin C., Straube A. Microtubules in cell migration. Essays Biochem. 2019 Oct; 63 (5): 509–520. |
| [19] | Hicks-Berthet J., Varelas X. Integrin-FAK-CDC42-PP1A signaling gnaws at YAP/TAZ activity to control incisor stem cells. Bioessays. 2017; 39 (10): 10. |
| [20] | Hou N., Wen Y., Yuan X. ET AL. Activation of Yap1/Taz signaling in ischemic heart disease and dilated cardiomyopathy. Exp Mol PathoL. 2017; 103 (3): 267-275. |
| [21] | Ruan Y. C., Wang Y., Da Silva N. CFTR interacts with ZO-1 to regulate tight junction assembly and epithelial differentiation through the ZONAB pathway. J Cell Sci. 2014; 127 (Pt 20): 4396-408. |
| [22] | Zihni C., Mills C., Matter K. Tight junctions: from simple barriers to multifunctional molecular Gates. Nat Rev Mol Cell Biol. (2016); 17, 564–580. |
| [23] | Balda M. S., Matter K. The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression EMBO J. 2000 May 2; 19 (9): 2024–2033. |
| [24] | Ikeda W., Nakanishi H., Miyoshi J. ET AL. Afadin: A key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis J Cell Biol 1999; 146 (5): 1117-32. |
| [25] | Aronson B. E., Stapleton K. A., Krasinski S. D. Role of GATA factors in development, differentiation, and homeostasis of the small intestinal epithelium Am J Physiol Gastrointest Liver Physiol. 2014; 306 (6): G474-90. |
| [26] | Kourtidis A., Ngok S. P., Anastasiadis P. Z. p120 catenin: an essential regulator of cadherin stability, adhesion-induced signaling, and cancer progression. Prog Mol Biol Transl Sci. 2013; 116: 409–432. |
| [27] | Greene c., Hanley n., Campbell m. Claudin-5: Gatekeeper of neurological function fluids Barriers CNS 2019; 16 (1): 3. |
| [28] | Mikels A. J., Nusse R. Wnts as ligand: processing, secretion and reception. Oncogene 2006; 25 (57): 7461-8. |
| [29] | Musgrove E. A. Wnt signalling via the epidermal growth factor receptor: a role in breast cancer? Breast Cancer Res. 2004; 6 (2): 65–68. |
| [30] | Kriz V., Korinek V. Wnt, RSPO and Hippo Signalling in the Intestine and Intestinal Stem Cells. Genes (Basel). 2018 Jan; 9 (1): 20. |
| [31] | Pataki C. A., Couchman J. R., Brábek J. Wnt Signaling Cascades and the Roles of Syndecan Proteoglycans. J Histochem Cytochem 2015; 63 (7): 465-80. |
| [32] | Cook A. A. Deng W., Ren J. Calcium-induced structural rearrangements release autoinhibition in the Rap-GEF CalDAG-GEFI. J Biol Chem 2018; 293 (22): 8521-8529. |
| [33] | Wilson S. R., Thé L., Batia L. M., The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch Cell 2013; 155 (2): 285-95. |
| [34] | Sharma M., Pruitt K. Wnt Pathway: An Integral Hub for Developmental and Oncogenic Signaling Networks Int J Mol Sci 2020; 21 (21): 8018. |
| [35] | Jia X, Zhang H., Cao X. ET AL. Activation of TRPV1 mediates thymic stromal lymphopoietin release via the Ca2+/NFAT pathway in airway epithelial cells FEBS Lett 2014; 588 (17): 3047-54. |
| [36] | Reynolds A. B., Roczniak-Ferguson A. Emerging roles for p120-catenin in cell adhesion and cancer Oncogene 2004; 23 (48): 7947-56. |
| [37] | Morgan R. G., Mortensson E, Williams A. C. Targeting LGR5 in Colorectal Cancer: therapeutic gold or too plastic? Br J Cancer 2018; 118 (11): 1410-1418. |
| [38] | Tian X, Liu Z, Niu B et al. E-Cadherin/β-Catenin Complex and the Epithelial Barrier J Biomed Biotechnol 2011; 2011: 567305. |
| [39] | Collinet C., Lecuit T. Stability and dynamics of cell-cell junctions. Prog Mol Biol Transl Sci 2013; 116: 25-47. |
| [40] | Rogan M. R., Patterson L. L., Wang J. Y. McBride J. W. Bacterial Manipulation of Wnt Signaling: A Host-Pathogen Tug-of-Wnt Front Immunol. 2019; 10: 2390. |
| [41] | Villarroel A., Valle-Pérez B. D., Fuerte S G. et al.. Src and Fyn define a new signaling cascade activated by canonical and non-canonical Wnt ligands and required for gene transcription and cell invasion. Cell Mol Life Sci 2020; 77 (5): 919-935. |
| [42] | Chen C-J, Liu Y-P. MERTK Inhibition: Potential as a Treatment Strategy in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer. Pharmaceuticals (Basel) 2021; 14 (2): 130. |
| [43] | Cestra G., Kwiatkowski A., Salazar M. et al. Tuba, a GEF for CDC42, links dynamin to actin regulatory proteins Methods Enzymol 2005; 404: 537-45. |
| [44] | Al-Bassam J., Chang F. Regulation of microtubule dynamics by TOG-domain proteins XMAP215/Dis1 and CLASP. Trends Cell Biol 2011; 21 (10): 604-14. |
| [45] | Zihni C., Munro P. M. G., Elbediwy A. ET AL. Dbl3 drives Cdc42 signaling at the apical margin to regulate junction position and apical differentiation. J Cell Biol. 2014 Jan 6; 204 (1): 111–127. |
| [46] | Lin D., Edwards A. S, Fawcett J. S., A mammalian PAR-3–PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity Nature Cell Biology (2000); 2, 540–547. |
| [47] | Aijaz S., D'Atri F., Citi S. ET AL. Binding of GEF-H1 to the tight junction-associated adaptor cingulin results in inhibition of Rho signaling and G1/S phase transition. Dev Cell 2005115; 8 (5): 777-86. |
| [48] | Díaz-Coránguez M., Liu X., Antonetti D. A. Tight Junctions in Cell Proliferation Int J Mol Sci 2019; 20 (23): 5972. |
| [49] | Rafiq N. B. M., Nishimura Y., Plotnikov S. V. A mechano-signalling network linking microtubules, myosin IIA filaments and integrin-based adhesions Nat Mater 2019; 18 (6): 638-649. |
| [50] | YoshimurA Y. Miki H. Dynamic regulation of GEF-H1 localization at microtubules by Par1b/MARK2. Biochem Biophys Res Commun 2011 May 6; 408 (2): 322-8. |
| [51] | Zihni C., Terry S. J. RhoGT Pase signalling at epithelial tight junctions: Bridging the GAP between polarity and cancer. Int J Biochem Cell Biol 2015; 64: 120-5. |
| [52] | Akhmanova A., Steinmetz M. O. Microtubule +TIPs at a glance. J Cell Sci 2010; 123 (Pt 20): 3415-9. |
| [53] | Harjunpää H., Asens M. L., Guenther C., Fagerholm S. C. Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment. Front Immunol 2019; 10: 1078. |
| [54] | Corr S. C., Palsson-McDermott E. M., Grishina I. MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C. Mucosal Immunology (2014); 7, 57–67. |
| [55] | Terry S. J., Zihni C., Elbediwy A. Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis. Nat Cell Biol 2011; 13 (2): 159-66. |
| [56] | Terry S. J., Elbediwy A., Zihni C. Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion. PLoS One 2012; 7 (11): e50188. |
| [57] | Baumgarth N. The double life of a B-1 cell: self-reactivity selects for protective effector functions. Nature Reviews Imm 2011; 11, 34–46. |
| [58] | Iwamoto N., Higashi T., Furuse M. Localization of angulin-1/LSR and tricellulin at tricellular contacts of brain and retinal endothelial cells in vivo. Cell Struct Funct 2014; 39 (1): 1-8. |
| [59] | Han P., Lei Y., Li D. Ten years of research on the role of BVES/ POPDC1 in human disease: a review. Onco Targets Ther. 2019; 12: 1279–1291. |
| [60] | Parang B., Thompson J. J., Williams C. S. Blood Vessel Epicardial Substance (BVES) in junctional signaling and cancer. Tissue Barriers 2018; 6 (4): 1–12. |
| [61] | Cario E., Podolsky D. K. Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 2000; 68 (12): 7010-7. |
| [62] | Wosen J. E., Mukhopadhyay D, Macaubas C., Mellins E. D. Epithelial MHC Class II Expression and Its Role in Antigen Presentation in the Gastrointestinal and Respiratory Tracts. Front Immunol 2018; 9: 2144. |
| [63] | Beyaz S., Chung C., Mou H. et al. Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis. Cell Stem Cell 2021 Nov 4; 28 (11): 1922-1935. e5. |
| [64] | Li Y-Y., Ishihara S., Aziz M. M. Autophagy is required for toll-like receptor-mediated interleukin-8 production in intestinal epithelial cells Int J Mol Med 2011; 27 (3): 337-44. |
| [65] | Fernandes P., O'Donnell C., LyonS C. Intestinal expression of Fas and Fas ligand is upregulated by bacterial signaling through TLR4 and TLR5, with activation of Fas modulating intestinal TLR-mediated inflammation J Immunol 2014; 193 (12): 6103-13. |
| [66] | Hocevar B. A., Brown T. L., Howe P. H. TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway. EMBO J 1999; 18 (5): 1345-56. |
| [67] | Dennler S., Prunier C., Ferrand N. ET AL. c-Jun inhibits transforming growth factor beta-mediated transcription by repressing Smad3 transcriptional activity J Biol Chem 2000; 275 (37): 28858-65. |
| [68] | Zhang X., Liu S., Wang Y. Interleukin-22 regulates the homeostasis of the intestinal epithelium during inflammation Int J Mol Med. 2019 Apr; 43 (4): 1657–1668. |
| [69] | Papoutsopoulou S., Pollock L., Walker C. ET AL. Impact of Interleukin 10 Deficiency on Intestinal Epithelium Responses to Inflammatory Signals Front Immunol 2021; 12: 690817. |
| [70] | Nakano N., Nishiyama C., Yagita H. ET AL. Notch1-mediated Signaling Induces MHC Class II Expression through Activation of Class II Transactivator Promoter III in Mast Cells. J Biol Chem. 2011; 286 (14): 12042–12048. |
| [71] | Houri N., Huang K-C., Nalbantoglu J. The Coxsackievirus and Adenovirus Receptor (CAR) undergoes ectodomain shedding and regulated intramembrane proteolysis (RIP) PLoS One 2013; 8 (8): e73296. |
| [72] | Wang Z., Li Y., Kong D., Sarkar F. H. The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness. Curr Drug Targets 2010; 11 (6): 745-51. |
| [73] | Walker E. M., Thompson C. A., Battle M. A. GATA4 and GATA6 regulate intestinal epithelial cytodifferentiation during development Dev Biol 2014; 392 (2): 283-94. |
| [74] | Song N., Scholtemeijer M., Shah K. Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential. Trends Pharmacol Sci 2020; 41 (9): 653-664. |
| [75] | Koliaraki V., Pallangyo C. K., Greten F. R., Kollias G. Mesenchymal Cells in Colon Cancer. Gastroenterology 201; 152 (5): 964-979. |
| [76] | Wang L., Zhao Y., Shi S. Interplay between mesenchymal stem cells and lymphocytes: implications for immunotherapy and tissue regeneration J Dent Res 2012; 91 (11): 1003-10. |
| [77] | Yu S., Zhou X., Steinke S. C. ET AL. The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy Immunity 2012; 37 (5): 813-26. |
| [78] | Taghon T., Rothenberg E. V. Molecular mechanisms that control mouse and human TCR-alphabeta and TCR-gammadelta T cell development. Semin Immunopathol 2008; 30 (4): 383-98. |
| [79] | 99. Ortega-Velázquez R., Díez-Marqués M. L., Ruiz-Torres M. P. ET AL. Arg-Gly-Asp-Ser (RGDS) peptide stimulates transforming growth factor beta1 transcription and secretion through integrin activation. FASEB J 2003; 17 (11): 1529-31. |
| [80] | Van de Walle I., Waegemans E., De Medts J. ET AL Specific Notch receptor-ligand interactions control human TCR-αβ/γδ development by inducing differential Notch signal strength. J Exp Med 2013; 210 (4): 683-97. |
| [81] | Jiang Q., Coffield V. M., Kondo M., Su L. TSLP is involved in expansion of early thymocyte progenitors BMC Immunology 2007; 8, 11. |
| [82] | Kulkarni N., Pathak M., Lal G. Role of chemokine receptors and intestinal epithelial cells in the mucosal inflammation and tolerance J Leukoc Biol 2017; 101 (2): 377-394. |
| [83] | Komban R. J., Strömberg A., Biram A. et al. Activated Peyer′s patch B cells sample antigen directly from M cells in the subepithelial dome. Nature Comm 2019; 10, 2423. |
| [84] | Kawahara T., Ohdan H., Zhao G. et al. Peritoneal cavity B cells are precursors of splenic IgM natural antibody-producing cells J Immunol 2003; 171 (10): 5406-14. |
| [85] | Zimmerman N. P., Vongsa R. A., Wendt M. K., Dwinell M. B. Chemokines and chemokine receptors in mucosal homeostasis at the intestinal epithelial barrier in inflammatory bowel disease. Inflamm Bowel Dis. 2008 Jul; 14 (7): 1000–1011. |
| [86] | Bukhari A. M. IgM+IgD− B cells in Human GALT Harbor Characteristics of B1 B cells. J Immunol 2020; 204 (1 Supplement) 158. 14. |
| [87] | Konjar S., Ferreira C., Blankenhaus B., Veldhoen M. Intestinal Barrier Interactions with Specialized CD8 T Cells Front Immunol 2017; 8: 1281. |
| [88] | Witherden D. A., Johnson M. D, Havran W. L. Coreceptors and Their Ligands in Epithelial γδ T Cell Biology Front Immunol. 2018; 9: 731. |
| [89] | Vantourout P., Vermijlen D., Pennington D. J. eds. (2019). Molecular Determinants of γδ T Cell Selection, Maintenance and Function. Lausanne: Frontiers. |
| [90] | Jiang L., ShaO Y., TiaN Y. et al. Nuclear Alarmin Cytokines in Inflammation. J Immunol Res. 2020; 7206451. |
| [91] | Panda S. K., Colonna M. Innate Lymphoid Cells in Mucosal Immunity. Front Immunol 2019 May 7; 10: 861. |
| [92] | Scanlon K. M., Hawksworth R. J., Lane S. J., Mahon B. P. IL-17A induces CCL28, supporting the chemotaxis of IgE-secreting B cells. Int Arch Allergy Immunol 2011; 156 (1): 51-61. |
| [93] | Isobe J., Maeda S., Obata Y. et al. Commensal-bacteria-derived butyrate promotes the T-cell-independent IgA response in the colon. Int Immunol. 2020; 32 (4): 243-258. |
APA Style
Meral Simsek. (2023). The Role of Intestinal Epithelial Cell Signaling In Mucosal Immunity. Cell Biology, 10(2), 41-52. https://doi.org/10.11648/j.cb.20221002.11
ACS Style
Meral Simsek. The Role of Intestinal Epithelial Cell Signaling In Mucosal Immunity. Cell Biol. 2023, 10(2), 41-52. doi: 10.11648/j.cb.20221002.11
AMA Style
Meral Simsek. The Role of Intestinal Epithelial Cell Signaling In Mucosal Immunity. Cell Biol. 2023;10(2):41-52. doi: 10.11648/j.cb.20221002.11
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.cb.20221002.11,
author = {Meral Simsek},
title = {The Role of Intestinal Epithelial Cell Signaling In Mucosal Immunity},
journal = {Cell Biology},
volume = {10},
number = {2},
pages = {41-52},
doi = {10.11648/j.cb.20221002.11},
url = {https://doi.org/10.11648/j.cb.20221002.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cb.20221002.11},
abstract = {In the words of Hippocrates, all disease begin in the gut. In the intestinal lumen, there are more than 1000 species of microbiota members containing 600,000 genes. that is 10 times more than the number of nucleated cells in our body. Connections such as tight junction (TJ) and adherens junction (AJ) between epithelial cells prevent the passage of microorganisms and antigens to the lamina proprea, while transmitting the received stimuli with signaling mechanisms. Integrin and immunoglobulin like adhesion molecules, which are members of the tight junction, receive signaling with ErbB (Her1, EGFR/2/3) and cytokine receptors (transforming growth factor TGFβ receptors) and transmit them to the nucleus, creating signals for gene transcription, proliferation, differentiation, cytokine synthesis, synthesis of surface receptors, epithelial mesenchimal transition (Emt) regulation, or apoptosis and growth arrest. Tight junction transmembrane proteins, scaffolding proteins such as zonulin, communicate with afadin-mediated AJ, allowing signals to be transmitted to the cytoskeleton. It makes gene expression with the transcription factor to which it is attached. It contributes to the ion balance with claudin, cytoskeleton regulation with occludin, gene transcription and cytokine synthesis with Marveld3, from the members of the TAMPs family to which it is linked. The stimulated cell synthesizes Wingless-ınt1 (Wnt) signaling molecules and performs paracrine and autocrine signaling. It balances intracellular Ca+2 level with non-canonical Wnt pathway, provides cell polarity especially via Cell division control protein 42 (CDC42) with non-canonical polarity pathway, β-catenin mediated gene transcription with canonical Wnt pathway. While microbial antigens are recognized by Toll like receptors (TLR) and cytokines are synthesized, antigen molecule presentation is regulated by major histocompatibility complex (Mhc) molecules. Cytokines synthesized by signaling trigger innate immunity in the lamina propria (LP) and adaptive immunity consisting of 50x109 lymphocytis, thereby initiating the anti-inflammatory or pro-inflammatory process. This review describes all these mechanisms and their connections.},
year = {2023}
}
TY - JOUR T1 - The Role of Intestinal Epithelial Cell Signaling In Mucosal Immunity AU - Meral Simsek Y1 - 2023/01/10 PY - 2023 N1 - https://doi.org/10.11648/j.cb.20221002.11 DO - 10.11648/j.cb.20221002.11 T2 - Cell Biology JF - Cell Biology JO - Cell Biology SP - 41 EP - 52 PB - Science Publishing Group SN - 2330-0183 UR - https://doi.org/10.11648/j.cb.20221002.11 AB - In the words of Hippocrates, all disease begin in the gut. In the intestinal lumen, there are more than 1000 species of microbiota members containing 600,000 genes. that is 10 times more than the number of nucleated cells in our body. Connections such as tight junction (TJ) and adherens junction (AJ) between epithelial cells prevent the passage of microorganisms and antigens to the lamina proprea, while transmitting the received stimuli with signaling mechanisms. Integrin and immunoglobulin like adhesion molecules, which are members of the tight junction, receive signaling with ErbB (Her1, EGFR/2/3) and cytokine receptors (transforming growth factor TGFβ receptors) and transmit them to the nucleus, creating signals for gene transcription, proliferation, differentiation, cytokine synthesis, synthesis of surface receptors, epithelial mesenchimal transition (Emt) regulation, or apoptosis and growth arrest. Tight junction transmembrane proteins, scaffolding proteins such as zonulin, communicate with afadin-mediated AJ, allowing signals to be transmitted to the cytoskeleton. It makes gene expression with the transcription factor to which it is attached. It contributes to the ion balance with claudin, cytoskeleton regulation with occludin, gene transcription and cytokine synthesis with Marveld3, from the members of the TAMPs family to which it is linked. The stimulated cell synthesizes Wingless-ınt1 (Wnt) signaling molecules and performs paracrine and autocrine signaling. It balances intracellular Ca+2 level with non-canonical Wnt pathway, provides cell polarity especially via Cell division control protein 42 (CDC42) with non-canonical polarity pathway, β-catenin mediated gene transcription with canonical Wnt pathway. While microbial antigens are recognized by Toll like receptors (TLR) and cytokines are synthesized, antigen molecule presentation is regulated by major histocompatibility complex (Mhc) molecules. Cytokines synthesized by signaling trigger innate immunity in the lamina propria (LP) and adaptive immunity consisting of 50x109 lymphocytis, thereby initiating the anti-inflammatory or pro-inflammatory process. This review describes all these mechanisms and their connections. VL - 10 IS - 2 ER -
Email: