{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:25:05Z","timestamp":1787019905253,"version":"build-2736575974"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL076179 and R35GM118337"],"award-info":[{"award-number":["R01HL076179 and R35GM118337"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gut-liver crosstalk exacerbates hepatic injury in gut ischemia\/reperfusion (I\/R), but its mechanism and therapeutic intervention remain elusive. Given the important roles of neutrophils and gut-resident intraepithelial lymphocytes (IELs) during acute inflammation, we hypothesized that the interaction between these two cell types worsens liver injury during gut I\/R.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Gut I\/R was induced in mice by occluding superior mesenteric artery (SMA) for 60\u00a0min, followed by 4\u00a0h resuscitation. Blood, intestine and liver tissues were collected for various analysis. Neutrophil extracellular traps (NETs) were determined by microscopy. Gut I\/R mice were injected (i.p.) with DPX2 (1\u00a0\u00b5g\/g BW) at the time of reperfusion. After 4\u00a0h, blood and liver tissues were collected for various analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We discovered that neutrophils in contact with IELs in gut I\/R mice had increased ability to form NETs. As such, NETs\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils were increased in the portal vein blood of gut I\/R mice compared to sham mice and the systemic blood, accompanied by increased NETs in the liver, indicating the migration of the activated neutrophils from the gut to the liver. Adoptive transfer of IEL-primed neutrophils into gut I\/R mice exacerbated liver inflammation as indicated by increased liver tissue levels of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), interleukin-1 beta (IL-1\u03b2), keratinocyte-derived chemokine (KC), and C-X-C motif chemokine ligand 2 (CXCL2). The interaction of neutrophils and IELs is known to be mediated via neutrophil CD112. Increased numbers of CD112\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils were observed in the gut epithelium after gut I\/R. We have discovered a CD112-derived peptide, named DPX2, which inhibits the interaction between CD112 on neutrophils and its proinflammatory ligand CD226 on IELs. In vitro, DPX2 attenuated IEL-induced NETosis under inflammatory conditions. In vivo, the administration of DPX2 significantly decreased NET-forming neutrophils in the portal vein of gut I\/R mice. In parallel to NETs inhibition, DPX2 administration significantly mitigated the gene expression of iNOS, IL-6, IL-1\u03b2, KC, and CXCL2 in the liver. Furthermore, the administration of DPX2 significantly attenuated liver injury as indicated by decreased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), tissue injury score, and liver cell death.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Neutrophil-gut IEL interaction mediates proinflammatory gut-liver crosstalk and the novel CD112-derived peptide DPX2 targeting this interaction has the potential to mitigate hepatic injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10020-026-01426-3","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:32:57Z","timestamp":1771338777000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel CD112-derived peptide targeting gut-primed neutrophils to attenuate deadly hepatic injury"],"prefix":"10.1186","volume":"32","author":[{"given":"Takayuki","family":"Kato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Murao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alok","family":"Jha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaifeng","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monowar","family":"Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"issue":"3","key":"1426_CR5","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","volume":"72","author":"A Albillos","year":"2020","unstructured":"Albillos A, De Gottardi A, Rescigno M. The gut-liver axis in liver disease: pathophysiological basis for therapy. J Hepatol. 2020;72(3):558\u201377. https:\/\/doi.org\/10.1016\/j.jhep.2019.10.003.","journal-title":"J Hepatol"},{"issue":"30","key":"1426_CR7","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1146\/annurev-immunol-020711-074942","volume":"30","author":"B Amulic","year":"2012","unstructured":"Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A. Neutrophil Function: From Mechanisms to Disease. Annu Rev Immunol. 2012;30(30):459\u2013489. https:\/\/doi.org\/10.1146\/annurev-immunol-020711-074942","journal-title":"Annu Rev Immunol"},{"issue":"9","key":"1426_CR37","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1056\/NEJMoa1705716","volume":"378","author":"D Annane","year":"2018","unstructured":"Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med. 2018;378(9):809\u201318. https:\/\/doi.org\/10.1056\/NEJMoa1705716.","journal-title":"N Engl J Med"},{"issue":"6606","key":"1426_CR45","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1126\/science.abg5645","volume":"377","author":"D Bousbaine","year":"2022","unstructured":"Bousbaine D, Fisch LI, London M, et al. A conserved bacteroidetes antigen induces anti-inflammatory intestinal T lymphocytes. Science. 2022;377(6606):660\u20136. https:\/\/doi.org\/10.1126\/science.abg5645.","journal-title":"Science"},{"issue":"4","key":"1426_CR36","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/nri.2017.1","volume":"17","author":"DW Cain","year":"2017","unstructured":"Cain DW, Cidlowski JA. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017;17(4):233\u201347. https:\/\/doi.org\/10.1038\/nri.2017.1.","journal-title":"Nat Rev Immunol"},{"issue":"7","key":"1426_CR14","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nri3007","volume":"11","author":"H Cheroutre","year":"2011","unstructured":"Cheroutre H, Lambolez F, Mucida D. The light and dark sides of intestinal intraepithelial lymphocytes. Nat Rev Immunol. 2011;11(7):445\u201356. https:\/\/doi.org\/10.1038\/nri3007.","journal-title":"Nat Rev Immunol"},{"issue":"4","key":"1426_CR8","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/nm1565","volume":"13","author":"SR Clark","year":"2007","unstructured":"Clark SR, Ma AC, Tavener SA, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007;13(4):463\u20139. https:\/\/doi.org\/10.1038\/nm1565.","journal-title":"Nat Med"},{"issue":"1","key":"1426_CR42","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1038\/s42003-022-03887-8","volume":"5","author":"D Dai","year":"2022","unstructured":"Dai D, Dai F, Chen J, et al. Integrated multi-omics reveal important roles of gut contents in intestinal ischemia\u2013reperfusion induced injuries in rats. Commun Biol. 2022;5(1):938. https:\/\/doi.org\/10.1038\/s42003-022-03887-8.","journal-title":"Commun Biol"},{"issue":"6","key":"1426_CR33","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/nri.2016.49","volume":"16","author":"S de Oliveira","year":"2016","unstructured":"de Oliveira S, Rosowski EE, Huttenlocher A. Neutrophil migration in infection and wound repair: going forward in reverse. Nat Rev Immunol. 2016;16(6):378\u201391. https:\/\/doi.org\/10.1038\/nri.2016.49.","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"1426_CR2","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1186\/s13054-022-04163-1","volume":"26","author":"A de Perez Ruiz","year":"2022","unstructured":"de Perez Ruiz A, Kortgen A, Leonhardt J, Zipprich A, Bauer M. Critical care hepatology: definitions, incidence, prognosis and role of liver failure in critically ill patients. Crit Care. 2022;26(1):289. https:\/\/doi.org\/10.1186\/s13054-022-04163-1.","journal-title":"Crit Care"},{"issue":"3","key":"1426_CR23","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.surg.2020.04.010","volume":"168","author":"NL Denning","year":"2020","unstructured":"Denning NL, Aziz M, Ochani M, Prince JM, Wang P. Inhibition of a triggering receptor expressed on myeloid cells-1 (TREM-1) with an extracellular cold-inducible RNA-binding protein (eCIRP)-derived peptide protects mice from intestinal ischemia-reperfusion injury. Surgery. 2020;168(3):478\u201385. https:\/\/doi.org\/10.1016\/j.surg.2020.04.010.","journal-title":"Surgery"},{"issue":"2","key":"1426_CR44","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1007\/s11739-023-03374-w","volume":"19","author":"F Di Vincenzo","year":"2024","unstructured":"Di Vincenzo F, Del Gaudio A, Petito V, Lopetuso LR, Scaldaferri F. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern Emerg Med. 2024;19(2):275\u201393. https:\/\/doi.org\/10.1007\/s11739-023-03374-w.","journal-title":"Intern Emerg Med"},{"key":"1426_CR48","doi-asserted-by":"publisher","first-page":"571085","DOI":"10.3389\/fimmu.2020.571085","volume":"11","author":"N Fine","year":"2020","unstructured":"Fine N, Tasevski N, McCulloch CA, Tenenbaum HC, Glogauer M. The neutrophil: constant defender and first responder. Front Immunol. 2020;11:571085. https:\/\/doi.org\/10.3389\/fimmu.2020.571085.","journal-title":"Front Immunol"},{"issue":"6","key":"1426_CR34","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1515\/hsz-2015-0309","volume":"397","author":"Y Hirano","year":"2016","unstructured":"Hirano Y, Aziz M, Wang P. Role of reverse transendothelial migration of neutrophils in inflammation. Biol Chem. 2016;397(6):497\u2013506. https:\/\/doi.org\/10.1515\/hsz-2015-0309.","journal-title":"Biol Chem"},{"issue":"6","key":"1426_CR1","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.1002\/hep.30824","volume":"70","author":"T Horvatits","year":"2019","unstructured":"Horvatits T, Drolz A, Trauner M, Fuhrmann V. Liver injury and failure in critical illness. Hepatology. 2019;70(6):2204. https:\/\/doi.org\/10.1002\/hep.30824.","journal-title":"Hepatology"},{"issue":"11","key":"1426_CR43","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/s41579-023-00904-3","volume":"21","author":"C Hsu","year":"2023","unstructured":"Hsu C, Schnabl B. The gut\u2013liver axis and gut microbiota in health and liver disease. Nat Rev Microbiol. 2023;21(11):719\u201333. https:\/\/doi.org\/10.1038\/s41579-023-00904-3.","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"1426_CR41","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s40168-022-01227-w","volume":"10","author":"J Hu","year":"2022","unstructured":"Hu J, Deng F, Zhao B, et al. Lactobacillus murinus alleviate intestinal ischemia\/reperfusion injury through promoting the release of interleukin-10 from M2 macrophages via Toll-like receptor 2 signaling. Microbiome. 2022;10(1):38. https:\/\/doi.org\/10.1186\/s40168-022-01227-w.","journal-title":"Microbiome"},{"issue":"6","key":"1426_CR21","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1097\/SLA.0000000000003167","volume":"272","author":"IHR Hundscheid","year":"2020","unstructured":"Hundscheid IHR, Schellekens DHSM, Grootjans J, et al. Females are more resistant to Ischemia-Reperfusion-induced intestinal injury than males: A human study. Ann Surg. 2020;272(6):1070\u20139. https:\/\/doi.org\/10.1097\/SLA.0000000000003167.","journal-title":"Ann Surg"},{"issue":"2","key":"1426_CR32","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1097\/SHK.0000000000002624","volume":"64","author":"K Ishikawa","year":"2025","unstructured":"Ishikawa K, Murao A, Murao T, Aziz M, Wang P. A multiple damage-associated molecular pattern\u2013scavenging compound OP18 attenuates hepatic ischemia\/reperfusion injury. Shock. 2025;64(2):265. https:\/\/doi.org\/10.1097\/SHK.0000000000002624.","journal-title":"Shock"},{"issue":"3","key":"1426_CR24","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1097\/SHK.0000000000001968","volume":"58","author":"M Kobritz","year":"2022","unstructured":"Kobritz M, Borjas T, Patel V, Coppa G, Aziz M, Wang P. H151, a small molecule inhibitor of STING as a novel therapeutic in intestinal ischemia-reperfusion injury. Shock. 2022;58(3):241\u201350. https:\/\/doi.org\/10.1097\/SHK.0000000000001968.","journal-title":"Shock"},{"issue":"3","key":"1426_CR6","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/nri3399","volume":"13","author":"E Kolaczkowska","year":"2013","unstructured":"Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13(3):159\u201375. https:\/\/doi.org\/10.1038\/nri3399.","journal-title":"Nat Rev Immunol"},{"issue":"3","key":"1426_CR30","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.jmb.2007.05.022","volume":"372","author":"E Krissinel","year":"2007","unstructured":"Krissinel E, Henrick K. Inference of macromolecular assemblies from crystalline state. J Mol Biol. 2007;372(3):774\u201397. https:\/\/doi.org\/10.1016\/j.jmb.2007.05.022.","journal-title":"J Mol Biol"},{"issue":"5","key":"1426_CR39","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1001\/jama.2024.24537","volume":"333","author":"PB Leung","year":"2025","unstructured":"Leung PB, Davis AM, Davis J. Corticosteroids for Sepsis, acute respiratory distress Syndrome, or Community-Acquired pneumonia. JAMA. 2025;333(5):421. https:\/\/doi.org\/10.1001\/jama.2024.24537.","journal-title":"JAMA"},{"issue":"2","key":"1426_CR16","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1002\/JLB.3RU0220-111","volume":"109","author":"H Ma","year":"2021","unstructured":"Ma H, Qiu Y, Yang H. Intestinal intraepithelial lymphocytes: maintainers of intestinal immune tolerance and regulators of intestinal immunity. J Leukoc Biol. 2021;109(2):339\u201347. https:\/\/doi.org\/10.1002\/JLB.3RU0220-111.","journal-title":"J Leukoc Biol"},{"issue":"4","key":"1426_CR26","doi-asserted-by":"publisher","first-page":"e20201665","DOI":"10.1084\/jem.20201665","volume":"218","author":"S Moon","year":"2021","unstructured":"Moon S, Park Y, Hyeon S, et al. Niche-specific MHC II and PD-L1 regulate CD4\u2009+\u2009CD8\u03b1\u03b1\u2009+\u2009intraepithelial lymphocyte differentiation. J Exp Med. 2021;218(4):e20201665. https:\/\/doi.org\/10.1084\/jem.20201665.","journal-title":"J Exp Med"},{"issue":"3","key":"1426_CR25","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/ni.2523","volume":"14","author":"D Mucida","year":"2013","unstructured":"Mucida D, Husain MM, Muroi S, et al. Transcriptional reprogramming of mature CD4\u2009+\u2009helper T cells generates distinct MHC class II\u2013restricted cytotoxic T lymphocytes. Nat Immunol. 2013;14(3):281\u20139. https:\/\/doi.org\/10.1038\/ni.2523.","journal-title":"Nat Immunol"},{"issue":"1","key":"1426_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-025-65572-8","volume":"16","author":"A Murao","year":"2025","unstructured":"Murao A, Jha A, Kato T, et al. Gut-primed neutrophils activate Kupffer cells to promote hepatic injury in mouse sepsis. Nat Commun. 2025;16(1):1\u201312. https:\/\/doi.org\/10.1038\/s41467-025-65572-8.","journal-title":"Nat Commun"},{"issue":"3","key":"1426_CR12","doi-asserted-by":"publisher","first-page":"310","DOI":"10.4049\/jimmunol.2200308","volume":"210","author":"K Murata","year":"2023","unstructured":"Murata K, Murao A, Aziz M, Wang P, Extracellular CIRP. Induces novel Nectin-2+ (CD112+) neutrophils to promote Th1 differentiation in sepsis. J Immunol. 2023;210(3):310\u201321. https:\/\/doi.org\/10.4049\/jimmunol.2200308.","journal-title":"J Immunol"},{"issue":"2","key":"1426_CR10","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/nri.2017.105","volume":"18","author":"V Papayannopoulos","year":"2018","unstructured":"Papayannopoulos V. Neutrophil extracellular traps in immunity and disease. Nat Rev Immunol. 2018;18(2):134\u201347. https:\/\/doi.org\/10.1038\/nri.2017.105.","journal-title":"Nat Rev Immunol"},{"issue":"W1","key":"1426_CR29","doi-asserted-by":"publisher","first-page":"W277","DOI":"10.1093\/nar\/gkab358","volume":"49","author":"C Quignot","year":"2021","unstructured":"Quignot C, Postic G, Bret H, et al. InterEvDock3: a combined template-based and free Docking server with increased performance through explicit modeling of complex homologs and integration of covariation-based contact maps. Nucleic Acids Res. 2021;49(W1):W277\u201384. https:\/\/doi.org\/10.1093\/nar\/gkab358.","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"1426_CR46","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1007\/s00134-016-4665-0","volume":"43","author":"A Reintam Blaser","year":"2017","unstructured":"Reintam Blaser A, Starkopf J, Alhazzani W, et al. Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines. Intensive Care Med. 2017;43(3):380\u201398. https:\/\/doi.org\/10.1007\/s00134-016-4665-0.","journal-title":"Intensive Care Med"},{"issue":"4","key":"1426_CR35","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/cdd.2011.1","volume":"18","author":"Q Remijsen","year":"2011","unstructured":"Remijsen Q, Kuijpers TW, Wirawan E, Lippens S, Vandenabeele P, Vanden Berghe T. Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality. Cell Death Differ. 2011;18(4):581\u20138. https:\/\/doi.org\/10.1038\/cdd.2011.1.","journal-title":"Cell Death Differ"},{"issue":"2","key":"1426_CR28","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1002\/prot.24728","volume":"83","author":"CEM Schindler","year":"2015","unstructured":"Schindler CEM, de Vries SJ, Zacharias M, iATTRACT. Simultaneous global and local interface optimization for protein\u2013protein Docking refinement. Proteins Struct Funct Bioinforma. 2015;83(2):248\u201358. https:\/\/doi.org\/10.1002\/prot.24728.","journal-title":"Proteins Struct Funct Bioinforma"},{"issue":"8","key":"1426_CR3","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801\u201310. https:\/\/doi.org\/10.1001\/jama.2016.0287.","journal-title":"JAMA"},{"issue":"6293","key":"1426_CR17","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1126\/science.aaf3892","volume":"352","author":"T Sujino","year":"2016","unstructured":"Sujino T, London M, van Hoytema DP, et al. Tissue adaptation of regulatory and intraepithelial CD4\u2009+\u2009T cells controls gut inflammation. Science. 2016;352(6293):1581\u20136. https:\/\/doi.org\/10.1126\/science.aaf3892.","journal-title":"Science"},{"issue":"6","key":"1426_CR31","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1097\/00007890-199306000-00011","volume":"55","author":"S Suzuki","year":"1993","unstructured":"Suzuki S, Toledo-Pereyra LH, Rodriguez FJ, Cejalvo D. Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine. Transplantation. 1993;55(6):1265\u201372. https:\/\/doi.org\/10.1097\/00007890-199306000-00011.","journal-title":"Transplantation"},{"issue":"11","key":"1426_CR4","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1016\/j.cmet.2022.09.017","volume":"34","author":"H Tilg","year":"2022","unstructured":"Tilg H, Adolph TE, Trauner M. Gut-liver axis: pathophysiological concepts and clinical implications. Cell Metab. 2022;34(11):1700\u201318. https:\/\/doi.org\/10.1016\/j.cmet.2022.09.017.","journal-title":"Cell Metab"},{"issue":"4","key":"1426_CR18","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.cell.2017.08.046","volume":"171","author":"DP van Hoytema","year":"2017","unstructured":"van Hoytema DP, Reis BS, Pedicord VA, Farache J, Victora GD, Mucida D. Intestinal epithelial and intraepithelial T cell crosstalk mediates a dynamic response to infection. Cell. 2017;171(4):783\u2013e79413. https:\/\/doi.org\/10.1016\/j.cell.2017.08.046.","journal-title":"Cell"},{"issue":"7","key":"1426_CR19","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.4049\/jimmunol.1701704","volume":"200","author":"L Van Kaer","year":"2018","unstructured":"Van Kaer L, Olivares-Villag\u00f3mez D. Development, Homeostasis, and functions of intestinal intraepithelial lymphocytes. J Immunol. 2018;200(7):2235\u201344. https:\/\/doi.org\/10.4049\/jimmunol.1701704.","journal-title":"J Immunol"},{"issue":"5","key":"1426_CR15","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/s41385-020-0294-6","volume":"13","author":"M Vandereyken","year":"2020","unstructured":"Vandereyken M, James OJ, Swamy M. Mechanisms of activation of innate-like intraepithelial T lymphocytes. Mucosal Immunol. 2020;13(5):721\u201331. https:\/\/doi.org\/10.1038\/s41385-020-0294-6.","journal-title":"Mucosal Immunol"},{"issue":"9","key":"1426_CR38","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1056\/NEJMoa1705835","volume":"378","author":"B Venkatesh","year":"2018","unstructured":"Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018;378(9):797\u2013808. https:\/\/doi.org\/10.1056\/NEJMoa1705835.","journal-title":"N Engl J Med"},{"issue":"7","key":"1426_CR40","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.3390\/cancers13071537","volume":"13","author":"S Walrand","year":"2021","unstructured":"Walrand S, Hesse M, d\u2019Abadie P, Jamar F. Hepatic arterial buffer response in liver radioembolization and potential use for improved cancer therapy. Cancers. 2021;13(7):1537. https:\/\/doi.org\/10.3390\/cancers13071537.","journal-title":"Cancers"},{"key":"1426_CR47","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41420-024-01891-x","volume":"10","author":"F Wang","year":"2024","unstructured":"Wang F, Huang H, Wei X, Tan P, Wang Z, Hu Z. Targeting cell death pathways in intestinal ischemia-reperfusion injury: a comprehensive review. Cell Death Discov. 2024;10:112. https:\/\/doi.org\/10.1038\/s41420-024-01891-x.","journal-title":"Cell Death Discov"},{"issue":"8","key":"1426_CR9","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/ni.2062","volume":"12","author":"A Woodfin","year":"2011","unstructured":"Woodfin A, Voisin MB, Beyrau M, et al. The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo. Nat Immunol. 2011;12(8):761\u20139. https:\/\/doi.org\/10.1038\/ni.2062.","journal-title":"Nat Immunol"},{"key":"1426_CR22","doi-asserted-by":"publisher","first-page":"649882","DOI":"10.3389\/fimmu.2021.649882","volume":"12","author":"M Wu","year":"2021","unstructured":"Wu M, Rowe JM, Fleming SD. Complement initiation varies by sex in intestinal ischemia reperfusion injury. Front Immunol. 2021;12:649882. https:\/\/doi.org\/10.3389\/fimmu.2021.649882.","journal-title":"Front Immunol"},{"issue":"1","key":"1426_CR27","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/nmeth.3213","volume":"12","author":"J Yang","year":"2015","unstructured":"Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y. The I-TASSER suite: protein structure and function prediction. Nat Methods. 2015;12(1):7\u20138. https:\/\/doi.org\/10.1038\/nmeth.3213.","journal-title":"Nat Methods"},{"issue":"16","key":"1426_CR11","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.1182\/blood-2013-04-457671","volume":"122","author":"BG Yipp","year":"2013","unstructured":"Yipp BG, Kubes P. NETosis: how vital is it? Blood. 2013;122(16):2784\u201394. https:\/\/doi.org\/10.1182\/blood-2013-04-457671.","journal-title":"Blood"},{"issue":"2","key":"1426_CR13","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1084\/jem.20150785","volume":"213","author":"Y Zhu","year":"2016","unstructured":"Zhu Y, Paniccia A, Schulick AC, et al. Identification of CD112R as a novel checkpoint for human T cells. J Exp Med. 2016;213(2):167\u201376. https:\/\/doi.org\/10.1084\/jem.20150785.","journal-title":"J Exp Med"}],"container-title":["Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-026-01426-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10020-026-01426-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-026-01426-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:22:57Z","timestamp":1781634177000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s10020-026-01426-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,17]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1426"],"URL":"https:\/\/doi.org\/10.1186\/s10020-026-01426-3","relation":{},"ISSN":["1528-3658"],"issn-type":[{"value":"1528-3658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,17]]},"assertion":[{"value":"25 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"25"}}