Characterization of Bovine Intraepithelial T Lymphocytes in the Gut
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cattle
2.2. Isolation of Cells from Lymph Nodes and Blood
2.3. T-IEL Isolation
2.4. Antibodies and Reagents
2.5. FACS
2.6. Statistical Analysis
3. Results
3.1. Similar Levels of TCRγδ+ and TCRαβ+ T Cells in Bovine T-IELs
3.2. TCRγδ+ T-IELs Are Dominantly CD8-Negative
3.3. TCRαβ+CD4+CD8αβ+ T Cells Are Substantial in T-IELs but Not in the Blood and Lymph Nodes
3.4. CD69 Is Highly Expressed in T-IELs, While CD62L Is Expressed at a Lower Level Compared to Their Counterparts in the Blood or Lymph Nodes
3.5. T-IELs Are Able to Produce Cytokines
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Olivares-Villagómez, D.; Van Kaer, L. Intestinal intraepithelial lymphocytes: Sentinels of the mucosal barrier. Trends Immunol. 2018, 39, 264–275. [Google Scholar] [CrossRef] [PubMed]
- Ma, H.; Qiu, Y.; Yang, H. Intestinal intraepithelial lymphocytes: Maintainers of intestinal immune tolerance and regulators of intestinal immunity. J. Leukoc. Biol. 2021, 109, 339–347. [Google Scholar] [CrossRef] [PubMed]
- Edelblum, K.L.; Singh, G.; Odenwald, M.A.; Lingaraju, A.; El Bissati, K.; Mcleod, R.; Sperling, A.I.; Turner, J.R. γδ intraepithelial lymphocyte migration limits transepithelial pathogen invasion and systemic disease in mice. Gastroenterology 2015, 148, 1417–1426. [Google Scholar] [CrossRef] [PubMed]
- Ismail, A.S.; Severson, K.M.; Vaishnava, S.; Behrendt, C.L.; Yu, X.; Benjamin, J.L.; Ruhn, K.A.; Hou, B.; Defranco, A.L.; Yarovinsky, F.; et al. γδ intraepithelial lymphocytes are essential mediators of host–microbial homeostasis at the intestinal mucosal surface. Proc. Natl. Acad. Sci. USA 2011, 108, 8743–8748. [Google Scholar] [CrossRef] [PubMed]
- Ismail, A.S.; Behrendt, C.L.; Hooper, L.V. Reciprocal interactions between commensal bacteria and gamma delta intraepithelial lymphocytes during mucosal injury. J. Immunol. 2009, 182, 3047–3054. [Google Scholar] [CrossRef] [PubMed]
- Dalton, J.E.; Cruickshank, S.M.; Egan, C.E.; Mears, R.; Newton, D.J.; Andrew, E.M.; Lawrence, B.; Howell, G.; Else, K.J.; Gubbels, M.J.; et al. Intraepithelial gammadelta+ lymphocytes maintain the integrity of intestinal epithelial tight junctions in response to infection. Gastroenterology 2006, 131, 818–829. [Google Scholar] [CrossRef] [PubMed]
- Boismenu, R.; Havran, W.L. Modulation of epithelial cell growth by intraepithelial gamma delta T cells. Science 1994, 266, 1253–1255. [Google Scholar] [CrossRef] [PubMed]
- Abrahamsen, M.S.; Lancto, C.A.; Walcheck, B.; Layton, W.; Jutila, M.A. Localization of α/β and γ/δ T lymphocytes in cryptosporidium parvum- infected tissues in naive and immune calves. Infect. Immun. 1997, 65, 2428–2433. [Google Scholar] [CrossRef]
- Fayer, R.; Gasbarre, L.; Pasquali, P.; Canals, A.; Almeria, S.; Zarlenga, D. Cryptosporidium parvum infection in bovine neonates: Dynamic clinical, parasitic and immunologic patterns. Int. J. Parasitol. 1998, 28, 49–56. [Google Scholar] [CrossRef]
- Menge, C.; Blessenohl, M.; Eisenberg, T.; Stamm, I.; Baljer, G. Bovine ileal intraepithelial lymphocytes represent target cells for shiga toxin 1 from escherichia coli. Infect. Immun. 2004, 72, 1896–1905. [Google Scholar] [CrossRef]
- Moussay, E.; Stamm, I.; Taubert, A.; Baljer, G.; Menge, C. Escherichia coli shiga toxin 1 enhances il-4 transcripts in bovine ileal intraepithelial lymphocytes. Vet. Immunol. Immunopathol. 2006, 113, 367–382. [Google Scholar] [CrossRef]
- Menge, C.; Stamm, I.; Van Diemen, P.M.; Sopp, P.; Baljer, G.; Wallis, T.S.; Stevens, M.P. Phenotypic and functional characterization of intraepithelial lymphocytes in a bovine ligated intestinal loop model of enterohaemorrhagic escherichia coli infection. J. Med. Microbiol. 2004, 53, 573–579. [Google Scholar] [CrossRef] [PubMed]
- Ludwig, L.; Egan, R.; Baquero, M.; Mansz, A.; Plattner, B.L. WC1(+) and WC1(neg) γδ T lymphocytes in intestinal mucosa of healthy and mycobacterium avium subspecies paratuberculosis-infected calves. Vet. Immunol. Immunopathol. 2019, 216, 109919. [Google Scholar] [CrossRef] [PubMed]
- Godson, D.L.; Campos, M.; Babiuk, L.A. Non-major histocompatibility complex-restricted cytotoxicity of bovine coronavirus-infected target cells mediated by bovine intestinal intraepithelial leukocytes. J. Gen. Virol. 1991, 72, 2457–2465. [Google Scholar] [CrossRef] [PubMed]
- Clough, E.R.; Dean, H.J. Isolation and characterization of lymphocytes from bovine intestinal epithelium and lamina propria. Vet. Immunol. Immunopathol. 1988, 19, 39–49. [Google Scholar] [CrossRef] [PubMed]
- Iwanaga, T.; Suzuki, Y.; Mori, K. Intraepithelial γδ T cells are closely associated with apoptotic enterocytes in the bovine intestine. Arch. Histol. Cytol. 1997, 60, 319–328. [Google Scholar] [CrossRef]
- Nagi, A.M.; Babiuk, L.A. Bovine gut-associated lymphoid tissue–morphologic and functional studies. I. Isolation and characterization of leukocytes from the epithelium and lamina propria of bovine small intestine. J. Immunol. Methods 1987, 105, 23–37. [Google Scholar] [CrossRef]
- Ray Waters, W.; Harp, J.A.; Nonnecke, B.J. Phenotypic analysis of peripheral blood lymphocytes and intestinal intra-epithelial lymphocytes in calves. Vet. Immunol. Immunopathol. 1995, 48, 249–259. [Google Scholar] [CrossRef]
- Waters, W.R.; Harp, J.A.; Nonnecke, B.J. In vitro blastogenic responses and interferon-γ production by intestinal intraepithelial lymphocytes of calves. Res. Vet. Sci. 1996, 61, 45–48. [Google Scholar] [CrossRef]
- Wyatt, C.R.; Barrett, W.J.; Brackett, E.J.; Davis, W.C.; Besser, T.E. Phenotypic comparison of ileal intraepithelial lymphocyte populations of suckling and weaned calves. Vet. Immunol. Immunopathol. 1999, 67, 213–222. [Google Scholar] [CrossRef]
- Almería, S.; Canals, A.; Zarlenga, D.S.; Gasbarre, L.C. Isolation and phenotypic characterization of abomasal mucosal lymphocytes in the course of a primary ostertagia ostertagi infection in calves. Vet. Immunol. Immunopathol. 1997, 57, 87–98. [Google Scholar] [CrossRef] [PubMed]
- Van Kaer, L.; Olivares-Villagómez, D. Development, homeostasis, and functions of intestinal intraepithelial lymphocytes. J. Immunol. 2018, 200, 2235–2244. [Google Scholar] [CrossRef] [PubMed]
- Denucci, C.C.; Mitchell, J.S.; Shimizu, Y. Integrin function in T-cell homing to lymphoid and nonlymphoid sites: Getting there and staying there. Crit. Rev.™ Immunol. 2009, 29, 87–109. [Google Scholar] [CrossRef] [PubMed]
- Edelblum, K.L.; Shen, L.; Weber, C.R.; Marchiando, A.M.; Clay, B.S.; Wang, Y.; Prinz, I.; Malissen, B.; Sperling, A.I.; Turner, J.R. Dynamic migration of γδ intraepithelial lymphocytes requires occludin. Proc. Natl. Acad. Sci. USA 2012, 109, 7097–7102. [Google Scholar] [CrossRef] [PubMed]
- Hu, M.D.; Ethridge, A.D.; Lipstein, R.; Kumar, S.; Wang, Y.; Jabri, B.; Turner, J.R.; Edelblum, K.L. Epithelial IL-15 Is a critical regulator of γδ intraepithelial lymphocyte motility within the intestinal mucosa. J. Immunol. 2018, 201, 747–756. [Google Scholar] [CrossRef] [PubMed]
- Lebrero-Fernández, C.; Bergström, J.H.; Pelaseyed, T.; Bas-Forsberg, A. Murine butyrophilin-like 1 and Btnl6 form heteromeric complexes in small intestinal epithelial cells and promote proliferation of local T lymphocytes. Front. Immunol. 2016, 7, 1. [Google Scholar] [CrossRef] [PubMed]
- Ma, L.J.; Acero, L.F.; Zal, T.; Schluns, K.S. Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8alphaalpha IELs. J. Immunol. 2009, 183, 1044–1054. [Google Scholar] [CrossRef] [PubMed]
- Hu, M.D.; Golovchenko, N.B.; Burns, G.L.; Nair, P.M.; Kelly, T.J., IV; Agos, J.; Irani, M.Z.; Soh, W.S.; Zeglinski, M.R.; Lemenze, A.; et al. γδ intraepithelial lymphocytes facilitate pathological epithelial cell shedding via CD103-mediated granzyme release. Gastroenterology 2022, 162, 877–889.e7. [Google Scholar] [CrossRef]
- Vantourout, P.; Laing, A.; Woodward, M.J.; Zlatareva, I.; Apolonia, L.; Jones, A.W.; Snijders, A.P.; Malim, M.H.; Hayday, A.C. Heteromeric interactions regulate butyrophilin (BTN) and BTN-like molecules governing γδ T cell biology. Proc. Natl. Acad. Sci. USA 2018, 115, 1039–1044. [Google Scholar] [CrossRef]
- Lodolce, J.P.; Boone, D.L.; Chai, S.; Swain, R.E.; Dassopoulos, T.; Trettin, S.; Ma, A. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 1998, 9, 669–676. [Google Scholar] [CrossRef]
- Ebert, E.C. Interleukin 15 is a potent stimulant of intraepithelial lymphocytes. Gastroenterology 1998, 115, 1439–1445. [Google Scholar] [CrossRef] [PubMed]
- ** thymocytes and in thymus-independent T cells. Immunity 1998, 9, 485–496. [Google Scholar] [CrossRef] [PubMed]
- Das, G.; Janeway, C.A., Jr. Development of CD8α/α and CD8α/β T cells in major histocompatibility complex class I–deficient mice. J. Exp. Med. 1999, 190, 881–884. [Google Scholar] [CrossRef]
- Guzman, E.; Hope, J.; Taylor, G.; Smith, A.L.; Cubillos-Zapata, C.; Charleston, B. Bovine gammadelta T cells are a major regulatory T cell subset. J. Immunol. 2014, 193, 208–222. [Google Scholar] [CrossRef]
- Hoek, A.; Rutten, V.P.M.G.; Kool, J.; Arkesteijn, G.J.A.; Bouwstra, R.J.; Van Rhijn, I.; Koets, A.P. Subpopulations of bovine WC1+γδ T cells rather than CD4+CD25highFoxp3+T cells act as immune regulatory cells ex vivo. Vet. Res. 2009, 40, 06. [Google Scholar] [CrossRef]
- Rhodes, S.G.; Hewinson, R.G.; Vordermeier, H.M. Antigen Recognition and Immunomodulation by γδ T Cells in Bovine Tuberculosis. J. Immunol. 2001, 166, 5604–5610. [Google Scholar] [CrossRef]
- Albarrak, S.M.; Waters, W.R.; Stabel, J.R.; Hostetter, J.M. Evaluating the cytokine profile of the WC1+ γδ T cell subset in the ileum of cattle with the subclinical and clinical forms of MAP infection. Vet. Immunol. Immunopathol. 2018, 201, 26–31. [Google Scholar] [CrossRef] [PubMed]
- Baldwin, C.L.; Telfer, J.C. The bovine model for elucidating the role of γδ T cells in controlling infectious diseases of importance to cattle and humans. Mol. Immunol. 2015, 66, 35–47. [Google Scholar] [CrossRef] [PubMed]
- Baldwin, C.L.; Yirsaw, A.; Gillespie, A.; Le Page, L.; Zhang, F.; Damani-Yokota, P.; Telfer, J.C. γδ T cells in livestock: Responses to pathogens and vaccine potential. Transbound. Emerg. Dis. 2020, 67, 119–128. [Google Scholar] [CrossRef] [PubMed]
- Bilate, A.M.; London, M.; Castro, T.B.R.; Mesin, L.; Bortolatto, J.; Kongthong, S.; Harnagel, A.; Victora, G.D.; Mucida, D. T Cell receptor is required for differentiation, but not maintenance, of intestinal CD4(+) intraepithelial lymphocytes. Immunity 2020, 53, 1001–1014.e20. [Google Scholar] [CrossRef] [PubMed]
- Su**o, T.; London, M.; Hoytema van Konijnenburg, D.P.; Rendon, T.; Buch, T.; Silva, H.M.; Lafaille, J.J.; Reis, B.S.; Mucida, D. Tissue adaptation of regulatory and intraepithelial CD4+ T cells controls gut inflammation. Science 2016, 352, 1581–1586. [Google Scholar] [CrossRef] [PubMed]
- Simpson, S.J.; Mizoguchi, E.; Allen, D.; Bhan, A.K.; Terhorst, C. Evidence that CD4+, but not CD8+ T cells are responsible for murine interleukin-2-deficient colitis. Eur. J. Immunol. 1995, 25, 2618–2625. [Google Scholar] [CrossRef] [PubMed]
- Pahar, B.; Lackner, A.A.; Veazey, R.S. Intestinal double-positive CD4+CD8+ T cells are highly activated memory cells with an increased capacity to produce cytokines. Eur. J. Immunol. 2006, 36, 583–592. [Google Scholar] [CrossRef]
- Mackay, L.K.; Braun, A.; Macleod, B.L.; Collins, N.; Tebartz, C.; Bedoui, S.; Carbone, F.R.; Gebhardt, T. Cutting edge: CD69 interference with sphingosine-1-phosphate receptor function regulates peripheral T cell retention. J. Immunol. 2015, 194, 2059–2063. [Google Scholar] [CrossRef]
- Radulovic, K.; Niess, J.H. CD69 is the crucial regulator of intestinal inflammation: A new target molecule for IBD treatment? J. Immunol. Res. 2015, 2015, 497056. [Google Scholar] [CrossRef]
- Zheng, M.Z.M.; Wakim, L.M. Tissue resident memory T cells in the respiratory tract. Mucosal Immunol. 2022, 15, 379–388. [Google Scholar] [CrossRef]
- Li, X.; Garcia, K.; Sun, Z.; **ao, Z. Temporal regulation of rapamycin on memory CTL programming by IL-12. PLoS ONE 2011, 6, e25177. [Google Scholar] [CrossRef] [PubMed]
- Mescher, M.F.; Agarwal, P.; Casey, K.A.; Hammerbeck, C.D.; **ao, Z.; Curtsinger, J.M. Molecular basis for checkpoints in the CD8 T cell response: Tolerance versus activation. Semin. Immunol. 2007, 19, 153–161. [Google Scholar] [CrossRef] [PubMed]
- Lauvau, G.; Soudja, S.M. Mechanisms of Memory T Cell Activation and Effective Immunity. Adv. Exp. Med. Biol. 2015, 850, 73–80. [Google Scholar] [CrossRef] [PubMed]
- Iezzi, G.; Karjalainen, K.; Lanzavecchia, A. The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity 1998, 8, 89–95. [Google Scholar] [CrossRef]
- Veldhoen, M.; Hocking, R.J.; Atkins, C.J.; Locksley, R.M.; Stockinger, B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 2006, 24, 179–189. [Google Scholar] [CrossRef] [PubMed]
- Li, L.; Ma, Y.; Xu, Y. Follicular regulatory T cells infiltrated the ovarian carcinoma and resulted in CD8 T cell dysfunction dependent on IL-10 pathway. Int. Immunopharmacol. 2019, 68, 81–87. [Google Scholar] [CrossRef]
- Liu, Y.; Rhoads, J.M. How does metabolism of an “immuno acid”(tryptophan) by commensal Lactobacillus reuteri educate resident intestinal intraepithelial lymphocytes? J. Lab. Precis. Med. 2018, 3, 46. [Google Scholar] [CrossRef]
- Pai, M.H.; Liu, J.J.; Yeh, S.L.; Chen, W.J.; Yeh, C.L. Glutamine modulates acute dextran sulphate sodium-induced changes in small-intestinal intraepithelial γδ-T-lymphocyte expression in mice. Br. J. Nutr. 2014, 111, 1032–1039. [Google Scholar] [CrossRef]
- Tung, J.N.; Lee, W.Y.; Pai, M.H.; Chen, W.J.; Yeh, C.L.; Yeh, S.L. Glutamine modulates CD8αα(+) TCRαβ(+) intestinal intraepithelial lymphocyte expression in mice with polymicrobial sepsis. Nutrition 2013, 29, 911–917. [Google Scholar] [CrossRef]
- Horio, Y.; Osawa, S.; Takagaki, K.; Hishida, A.; Furuta, T.; Ikuma, M. Glutamine supplementation increases Th1-cytokine responses in murine intestinal intraepithelial lymphocytes. Cytokine 2008, 44, 92–95. [Google Scholar] [CrossRef]
- Ishizuka, S.; Tanaka, S. Modulation of CD8+ intraepithelial lymphocyte distribution by dietary fiber in the rat large intestine1. Exp. Biol. Med. 2002, 227, 1017–1021. [Google Scholar] [CrossRef] [PubMed]
- Kim, C.H. Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids. Cell. Mol. Immunol. 2021, 18, 1161–1171. [Google Scholar] [CrossRef]
- Robles, E.F.; Vázquez, V.P.; Emiliano, J.R.; Amaro, R.G.; Briones, S.L. High fat diet induces alterations to intraepithelial lymphocyte and cytokine mRNA in the small intestine of C57BL/6 mice. RSC Adv. 2017, 7, 5322–5330. [Google Scholar] [CrossRef]
- Wang, J.; Zhang, H.; Ma, H.; Lu, B.; Wang, J.; Li, Y.; Li, J. Inhibitory effect of dietary n-3 polyunsaturated fatty acids to intestinal IL-15 expression is associated with reduction of TCRαβ+CD8α+CD8β− intestinal intraepithelial lymphocytes. J. Nutr. Biochem. 2008, 19, 475–481. [Google Scholar] [CrossRef] [PubMed]
- Veldhoen, M.; Ferreira, C. Influence of nutrient-derived metabolites on lymphocyte immunity. Nat. Med. 2015, 21, 709–718. [Google Scholar] [CrossRef]
- Chen, W.; Pu, A.; Sheng, B.; Zhang, Z.; Li, L.; Liu, Z.; Wang, Q.; Li, X.; Ma, Y.; Yu, M.; et al. Aryl hydrocarbon receptor activation modulates CD8αα(+)TCRαβ(+) IELs and suppression of colitis manifestations in mice. Biomed. Pharm. 2017, 87, 127–134. [Google Scholar] [CrossRef]
- Pinto, C.J.G.; Ávila-Gálvez, M.Á.; Lian, Y.; Moura-Alves, P.; Nunes dos Santos, C. Targeting the aryl hydrocarbon receptor by gut phenolic metabolites: A strategy towards gut inflammation. Redox Biol. 2023, 61, 102622. [Google Scholar] [CrossRef]
- Li, Y.; Innocentin, S.; Withers, D.R.; Roberts, N.A.; Gallagher, A.R.; Grigorieva, E.F.; Wilhelm, C.; Veldhoen, M. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 2011, 147, 629–640. [Google Scholar] [CrossRef]
- Zhang, Z.; Pu, A.; Yu, M.; **ao, W.; Sun, L.; Cai, Y.; Yang, H. Aryl hydrocarbon receptor activation modulates γδ intestinal intraepithelial lymphocytes and protects against ischemia/reperfusion injury in the murine small intestine. Mol. Med. Rep. 2019, 19, 1840–1848. [Google Scholar] [CrossRef]
- Nagafuchi, S.; Totsuka, M.; Hachimura, S.; Goto, M.; Takahashi, T.; Yajima, T.; Kuwata, T.; Kaminogawa, S. Dietary nucleotides increase the proportion of a tcrγδ+ Subset of intraepithelial lymphocytes (iel) and il-7 production by intestinal epithelial cells (iec); implications for modification of cellular and molecular cross-talk between iel and iec by dietary nucleotides. Biosci. Biotechnol. Biochem. 2000, 64, 1459–1465. [Google Scholar] [CrossRef]
- Minton, K. Negative regulation of AHR essential for intestinal homeostasis. Nat. Rev. Immunol. 2023, 23, 202. [Google Scholar] [CrossRef] [PubMed]
- Wyatt, C.R.; Brackett, E.J.; Perryman, L.E.; Davis, W.C. Identification of γδT lymphocyte subsets that populate calf ileal mucosa after birth. Vet. Immunol. Immunopathol. 1996, 52, 91–103. [Google Scholar] [CrossRef] [PubMed]
- Yasuda, M.; Ogawa, D.; Nasu, T.; Yamaguchi, T.; Murakami, T. Kinetics and distribution of bovine γδ T-lymphocyte in the intestine: γδ T cells accumulate in the dome region of Peyer’s patch during prenatal development. Dev. Comp. Immunol. 2005, 29, 555–564. [Google Scholar] [CrossRef] [PubMed]
- Hassan, H.; Sakaguchi, S.; Tenno, M.; Kopf, A.; Boucheron, N.; Carpenter, A.C.; Egawa, T.; Taniuchi, I.; Ellmeier, W. Cd8 enhancer E8I and Runx factors regulate CD8α expression in activated CD8+ T cells. Proc. Natl. Acad. Sci. USA 2011, 108, 18330–18335. [Google Scholar] [CrossRef] [PubMed]
- Walker, L.; Marrinan, E.; Muenchhoff, M.; Fergusson, J.; Kloverpris, H.; Cheroutre, H.; Barnes, E.; Goulder, P.; Klenerman, P. CD8αα expression marks terminally differentiated human CD8+ T cells expanded in chronic viral infection. Front. Immunol. 2013, 4, 223. [Google Scholar] [CrossRef] [PubMed]
- Cheroutre, H.; Lambolez, F. Doubting the TCR coreceptor function of CD8αα. Immunity 2008, 28, 149–159. [Google Scholar] [CrossRef] [PubMed]
- Wilson, E.; Hedges, J.F.; Butcher, E.C.; Briskin, M.; Jutila, M.A. Bovine γδ T cell subsets express distinct patterns of chemokine responsiveness and adhesion molecules: A mechanism for tissue-specific γδ T cell subset accumulation1. J. Immunol. 2002, 169, 4970–4975. [Google Scholar] [CrossRef]
- Costes, L.M.M.; Lindenbergh-Kortleve, D.J.; Van Berkel, L.A.; Veenbergen, S.; Raatgeep, H.C.; Simons-Oosterhuis, Y.; Van Haaften, D.H.; Karrich, J.J.; Escher, J.C.; Groeneweg, M.; et al. IL-10 signaling prevents gluten-dependent intraepithelial CD4+ cytotoxic T lymphocyte infiltration and epithelial damage in the small intestine. Mucosal Immunol. 2019, 12, 479–490. [Google Scholar] [CrossRef]
- Reis, B.S.; Rogoz, A.; Costa-Pinto, F.A.; Taniuchi, I.; Mucida, D. Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4+ T cell immunity. Nat. Immunol. 2013, 14, 271–280. [Google Scholar] [CrossRef]
- Konkel, J.E.; Maruyama, T.; Carpenter, A.C.; **ong, Y.; Zamarron, B.F.; Hall, B.E.; Kulkarni, A.B.; Zhang, P.; Bosselut, R.; Chen, W. Control of the development of CD8αα+ intestinal intraepithelial lymphocytes by TGF-β. Nat. Immunol. 2011, 12, 312–319. [Google Scholar] [CrossRef] [PubMed]
- Reis, B.S.; van Konijnenburg, D.P.H.; Grivennikov, S.I.; Mucida, D. Transcription factor T-bet regulates intraepithelial lymphocyte functional maturation. Immunity 2014, 41, 244–256. [Google Scholar] [CrossRef] [PubMed]
- Carton, J.; Byrne, B.; Madrigal-Estebas, L.; O’Donoghue, D.P.; O’Farrelly, C. CD4+CD8+ human small intestinal T cells are decreased in coeliac patients, with CD8 expression downregulated on intra-epithelial T cells in the active disease. Eur. J. Gastroenterol. Hepatol. 2004, 16, 961–968. [Google Scholar] [CrossRef] [PubMed]
- London, M.; Bilate, A.M.; Castro, T.B.R.; Su**o, T.; Mucida, D. Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program. Nat. Immunol. 2021, 22, 449–459. [Google Scholar] [CrossRef] [PubMed]
- Bhuyan, Z.A.; Rahman, M.A.; Maradana, M.R.; Mehdi, A.M.; Bergot, A.-S.; Simone, D.; El-Kurdi, M.; Garrido-Mesa, J.; Cai, C.B.B.; Cameron, A.J.; et al. Genetically encoded Runx3 and CD4+ intestinal epithelial lymphocyte deficiencies link SKG mouse and human predisposition to spondyloarthropathy. Clin. Immunol. 2023, 247, 109220. [Google Scholar] [CrossRef] [PubMed]
- Germain, R.N. T-cell development and the CD4–CD8 lineage decision. Nat. Rev. Immunol. 2002, 2, 309–322. [Google Scholar] [CrossRef] [PubMed]
- Bankovich, A.J.; Shiow, L.R.; Cyster, J.G. CD69 suppresses sphingosine 1-phosophate receptor-1 (S1P1) function through interaction with membrane helix 4. J. Biol. Chem. 2010, 285, 22328–22337. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Chen, S.; **ang, H.; Liang, Z.; Lu, H. Role of sphingosine-1-phosphate receptors in vascular injury of inflammatory bowel disease. J. Cell. Mol. Med. 2021, 25, 2740–2749. [Google Scholar] [CrossRef]
- Ji, T.; Xu, C.; Sun, L.; Yu, M.; Peng, K.; Qiu, Y.; **ao, W.; Yang, H. Aryl hydrocarbon receptor activation down-regulates IL-7 and reduces inflammation in a mouse model of dss-induced colitis. Dig. Dis. Sci. 2015, 60, 1958–1966. [Google Scholar] [CrossRef]
- Grailer, J.J.; Kodera, M.; Steeber, D.A. L-selectin: Role in regulating homeostasis and cutaneous inflammation. J. Dermatol. Sci. 2009, 56, 141–147. [Google Scholar] [CrossRef]
- La Scaleia, R.; Barba, M.; Di Nardo, G.; Bonamico, M.; Oliva, S.; Nenna, R.; Valitutti, F.; Mennini, M.; Barbato, M.; Montuori, M.; et al. Size and dynamics of mucosal and peripheral IL-17A+ T-cell pools in pediatric age, and their disturbance in celiac disease. Mucosal Immunol. 2012, 5, 513–523. [Google Scholar] [CrossRef]
- Paroni, M.; Magarotto, A.; Tartari, S.; Nizzoli, G.; Larghi, P.; Ercoli, G.; Gianelli, U.; Pagani, M.; Elli, L.; Abrignani, S.; et al. Uncontrolled IL-17 production by intraepithelial lymphocytes in a case of non-IPEX Autoimmune enteropathy. Clin. Transl. Gastroenterol. 2016, 7, e182. [Google Scholar] [CrossRef] [PubMed]
- Ruberti, M.; Fernandes, L.G.R.; Simioni, P.U.; Gabriel, D.L.; Yamada, A.T.; Tamashiro, W.M.d.S.C. Phenotypical and functional analysis of intraepithelial lymphocytes from small intestine of mice in oral tolerance. J. Immunol. Res. 2012, 2012, 208054. [Google Scholar]
- Monteleone, I.; Sarra, M.; Del Vecchio Blanco, G.; Paoluzi, O.A.; Franzè, E.; Fina, D.; Fabrizi, A.; MacDonald, T.T.; Pallone, F.; Monteleone, G. Characterization of IL-17A-producing cells in celiac disease mucosa. J. Immunol. 2010, 184, 2211–2218. [Google Scholar] [CrossRef] [PubMed]
- Lundqvist, C.; Melgar, S.; Yeung, M.M.; Hammarström, S.; Hammarström, M.L. Intraepithelial lymphocytes in human gut have lytic potential and a cytokine profile that suggest T helper 1 and cytotoxic functions. J. Immunol. 1996, 157, 1926–1934. [Google Scholar] [CrossRef] [PubMed]
- Wilharm, A.; Tabib, Y.; Nassar, M.; Reinhardt, A.; Mizraji, G.; Sandrock, I.; Heyman, O.; Barros-Martins, J.; Aizenbud, Y.; Khalaileh, A.; et al. Mutual interplay between IL-17–producing γδT cells and microbiota orchestrates oral mucosal homeostasis. Proc. Natl. Acad. Sci. USA 2019, 116, 2652–2661. [Google Scholar] [CrossRef] [PubMed]
- Yang, H.; Kiristioglu, I.; Fan, Y.; Forbush, B.; Bishop, D.K.; Antony, P.A.; Zhou, H.; Teitelbaum, D.H. Interferon-gamma expression by intraepithelial lymphocytes results in a loss of epithelial barrier function in a mouse model of total parenteral nutrition. Ann. Surg. 2002, 236, 226–234. [Google Scholar] [CrossRef] [PubMed]
- Barrett, T.A.; Gajewski, T.F.; Danielpour, D.; Chang, E.B.; Beagley, K.W.; Bluestone, J.A. Differential function of intestinal intraepithelial lymphocyte subsets. J. Immunol. 1992, 149, 1124–1130. [Google Scholar] [CrossRef]
- Mennechet, F.J.D.; Kasper, L.H.; Rachinel, N.; Minns, L.A.; Luangsay, S.; Vandewalle, A.; Buzoni-Gatel, D. Intestinal intraepithelial lymphocytes prevent pathogen-driven inflammation and regulate the Smad/T-bet pathway of lamina propria CD4+ T cells. Eur. J. Immunol. 2004, 34, 1059–1067. [Google Scholar] [CrossRef]
- Howe, K.L.; Reardon, C.; Wang, A.; Nazli, A.; Mckay, D.M. Transforming growth factor-β regulation of epithelial tight junction proteins enhances barrier function and blocks enterohemorrhagic escherichia coli O157:H7-induced increased permeability. Am. J. Pathol. 2005, 167, 1587–1597. [Google Scholar] [CrossRef] [PubMed]
- Ihara, S.; Hirata, Y.; Serizawa, T.; Suzuki, N.; Sakitani, K.; Kinoshita, H.; Hayakawa, Y.; Nakagawa, H.; Ijichi, H.; Tateishi, K.; et al. TGF-β signaling in dendritic cells governs colonic homeostasis by controlling epithelial differentiation and the luminal microbiota. J. Immunol. 2016, 196, 4603–4613. [Google Scholar] [CrossRef]
- Li, G.; Ren, J.; Hu, Q.; Deng, Y.; Chen, G.; Guo, K.; Li, R.; Li, Y.; Wu, L.; Wang, G.; et al. Oral pirfenidone protects against fibrosis by inhibiting fibroblast proliferation and TGF-β signaling in a murine colitis model. Biochem. Pharm. 2016, 117, 57–67. [Google Scholar] [CrossRef] [PubMed]
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Hada, A.; Li, L.; Kandel, A.; **, Y.; **ao, Z. Characterization of Bovine Intraepithelial T Lymphocytes in the Gut. Pathogens 2023, 12, 1173. https://doi.org/10.3390/pathogens12091173
Hada A, Li L, Kandel A, ** Y, **ao Z. Characterization of Bovine Intraepithelial T Lymphocytes in the Gut. Pathogens. 2023; 12(9):1173. https://doi.org/10.3390/pathogens12091173
Chicago/Turabian StyleHada, Akanksha, Lei Li, Anmol Kandel, Younggeon **, and Zhengguo **ao. 2023. "Characterization of Bovine Intraepithelial T Lymphocytes in the Gut" Pathogens 12, no. 9: 1173. https://doi.org/10.3390/pathogens12091173