Skip to content
2000
image of DNA Methylation-mediated BTN3A2 Regulation via CD14+CD16+ Monocytes Protects Against Primary Sclerosing Cholangitis
file format pdf download PDF

Abstract

Introduction

Primary Sclerosing Cholangitis (PSC) remains a significant challenge in hepatology with an unclear pathogenesis and limited treatment options. This study employed Mendelian Randomization (MR) to explore novel pathogenic mechanisms of PSC.

Methods

We analyzed publicly available datasets, including cis-eQTL, cis-pQTL, 731 immune cell profiles, DNA methylation data, and PSC GWAS summary statistics. Using Inverse Variance Weighted (IVW) as our primary method, we identified genes causally associated with PSC. Subsequent mediation analyses elucidated how DNA methylation regulates gene expression and how these genes influence PSC through specific immune cell subpopulations.

Results

Our analysis revealed a significant protective effect of BTN3A2 expression against PSC risk (IVW OR 0.838, 95% CI 0.792–0.887, 1.12E-09). Mediation analysis indicated that methylation at cg23465465 had a largely mediated effect on PSC risk through BTN3A2 regulation (89.3% mediated effect). Additionally, BTN3A2 exerted partial protection CD14+CD16+ monocytes (4.7% mediation).

Discussion

This study suggests a protective role for BTN3A2 in PSC pathogenesis, supported by reliable DNA methylation regulation. Although CD14+CD16+ monocytes had a minor impact, they provide new insights into the immune mechanisms of PSC. However, these findings require cautious interpretation pending experimental validation.

Conclusion

These findings identify BTN3A2 as a causal protective factor in PSC, mediated by DNA methylation and CD14+CD16+ monocyte-driven immunity, highlighting its therapeutic potential for precision medicine.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266423650251031072305
2026-01-05
2026-01-12

  • From This Site

    /content/journals/ctmc/10.2174/0115680266423650251031072305
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/ctmc/10.2174/0115680266423650251031072305/BMS-CTMC-2025-268.html?itemId=/content/journals/ctmc/10.2174/0115680266423650251031072305&mimeType=html&fmt=ahah

References

  1. Bowlus C.L. Arrivé L. Bergquist A. Deneau M. Forman L. Ilyas S.I. Lunsford K.E. Martinez M. Sapisochin G. Shroff R. Tabibian J.H. Assis D.N. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2023 77 2 659 702 10.1002/hep.32771 36083140
    [Google Scholar]
  2. Manns M.P. Bergquist A. Karlsen T.H. Levy C. Muir A.J. Ponsioen C. Trauner M. Wong G. Younossi Z.M. Primary sclerosing cholangitis. Nat. Rev. Dis. Primers 2025 11 1 17 10.1038/s41572‑025‑00600‑x 40082445
    [Google Scholar]
  3. Park J.W. Kim J.H. Kim S.E. Jung J.H. Jang M.K. Park S.H. Lee M.S. Kim H.S. Suk K.T. Kim D.J. Primary biliary cholangitis and primary sclerosing cholangitis: Current knowledge of pathogenesis and therapeutics. Biomedicines 2022 10 6 1288 10.3390/biomedicines10061288 35740310
    [Google Scholar]
  4. Nakamoto N. Sasaki N. Aoki R. Miyamoto K. Suda W. Teratani T. Suzuki T. Koda Y. Chu P.S. Taniki N. Yamaguchi A. Kanamori M. Kamada N. Hattori M. Ashida H. Sakamoto M. Atarashi K. Narushima S. Yoshimura A. Honda K. Sato T. Kanai T. Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis. Nat. Microbiol. 2019 4 3 492 503 10.1038/s41564‑018‑0333‑1 30643240
    [Google Scholar]
  5. Trivedi P.J. Crothers H. Mytton J. Bosch S. Iqbal T. Ferguson J. Hirschfield G.M. Effects of primary sclerosing cholangitis on risks of cancer and death in people with inflammatory bowel disease, based on sex, race, and age. Gastroenterology 2020 159 3 915 928 10.1053/j.gastro.2020.05.049 32445859
    [Google Scholar]
  6. Fuchs C.D. Trauner M. Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology. Nat. Rev. Gastroenterol. Hepatol. 2022 19 7 432 450 10.1038/s41575‑021‑00566‑7 35165436
    [Google Scholar]
  7. Luo X. Lu L.G. Progress in the management of patients with cholestatic liver disease: Where are we and where are we going? J. Clin. Transl. Hepatol. 2024 12 6 581 588 10.14218/JCTH.2023.00519 38974958
    [Google Scholar]
  8. Kuo A. Gomel R. Safer R. Lindor K.D. Everson G.T. Bowlus C.L. Characteristics and outcomes reported by patients with primary sclerosing cholangitis through an online registry. Clin. Gastroenterol. Hepatol. 2019 17 7 1372 1378 10.1016/j.cgh.2018.04.047 29705262
    [Google Scholar]
  9. Eliasson J. Lo B. Schramm C. Chazouilleres O. Folseraas T. Beuers U. Ytting H. Survey uncovering variations in the management of primary sclerosing cholangitis across Europe. JHEP Rep Innov. Hepatol. 2022 4 11 100553 10.1016/j.jhepr.2022.100553 36164416
    [Google Scholar]
  10. Yang H. Zhen J. Huang X. Chen M. Cui H. Sheng X. Li X. Current status of pharmacotherapy for primary sclerosing cholangitis. Front. Med. 2025 12 1544601 10.3389/fmed.2025.1544601 40655103
    [Google Scholar]
  11. Trauner M. Halilbasic E. Tatscher E. Fickert P. Primary sclerosing cholangitis—diagnosis and treatment 2024. Inn. Med. 2024 65 4 347 356 10.1007/s00108‑024‑01697‑0 38498179
    [Google Scholar]
  12. Dyson J.K. Beuers U. Jones D.E.J. Lohse A.W. Hudson M. Primary sclerosing cholangitis. Lancet 2018 391 10139 2547 2559 10.1016/S0140‑6736(18)30300‑3 29452711
    [Google Scholar]
  13. Davey Smith G. Hemani G. Mendelian randomization: Genetic anchors for causal inference in epidemiological studies. Hum. Mol. Genet. 2014 23 R1 R89 R98 10.1093/hmg/ddu328 25064373
    [Google Scholar]
  14. Emdin C.A. Khera A.V. Kathiresan S. Mendelian randomization. JAMA 2017 318 19 1925 1926 10.1001/jama.2017.17219 29164242
    [Google Scholar]
  15. Jiang D. Zheng S. Xu X. Yue H. Liang W. Wu Z. Uncovering druggable targets in aortic dissection: An association study integrating mendelian randomization, pQTL, and protein–protein interaction network. Biomedicines 2024 12 6 1204 10.3390/biomedicines12061204 38927411
    [Google Scholar]
  16. Zheng J. Haberland V. Baird D. Walker V. Haycock P.C. Hurle M.R. Gutteridge A. Erola P. Liu Y. Luo S. Robinson J. Richardson T.G. Staley J.R. Elsworth B. Burgess S. Sun B.B. Danesh J. Runz H. Maranville J.C. Martin H.M. Yarmolinsky J. Laurin C. Holmes M.V. Liu J.Z. Estrada K. Santos R. McCarthy L. Waterworth D. Nelson M.R. Smith G.D. Butterworth A.S. Hemani G. Scott R.A. Gaunt T.R. Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases. Nat. Genet. 2020 52 10 1122 1131 10.1038/s41588‑020‑0682‑6 32895551
    [Google Scholar]
  17. Suhre K. McCarthy M.I. Schwenk J.M. Genetics meets proteomics: Perspectives for large population-based studies. Nat. Rev. Genet. 2021 22 1 19 37 10.1038/s41576‑020‑0268‑2 32860016
    [Google Scholar]
  18. Dai L. Ye Y. Mugaany J. Hu Z. Huang J. Lu C. Leveraging pQTL-based Mendelian randomization to identify new treatment prospects for primary biliary cholangitis and primary sclerosing cholangitis. Aging 2024 16 10 9228 9250 10.18632/aging.205867 38809509
    [Google Scholar]
  19. Skrivankova V.W. Richmond R.C. Woolf B.A.R. Yarmolinsky J. Davies N.M. Swanson S.A. VanderWeele T.J. Higgins J.P.T. Timpson N.J. Dimou N. Langenberg C. Golub R.M. Loder E.W. Gallo V. Tybjaerg-Hansen A. Davey Smith G. Egger M. Richards J.B. Strengthening the reporting of observational studies in epidemiology using mendelian randomization. JAMA 2021 326 16 1614 1621 10.1001/jama.2021.18236 34698778
    [Google Scholar]
  20. Cheung A.C. Juran B.D. Schlicht E.M. McCauley B.M. Atkinson E.J. Moore R. Heimbach J.K. Watt K.D. Wu T.T. LaRusso N.F. Gores G.J. Sun Z. Lazaridis K.N. DNA methylation profile of liver tissue in end-stage cholestatic liver disease. Epigenomics 2022 14 8 481 497 10.2217/epi‑2021‑0343 35473391
    [Google Scholar]
  21. Luo P. Liu L. Hou W. Xu K. Xu P. Gene set enrichment analysis detected immune cell‐related pathways associated with primary sclerosing cholangitis. BioMed Res. Int. 2022 2022 1 2371347 10.1155/2022/2371347 36060137
    [Google Scholar]
  22. Võsa U. Claringbould A. Westra H.J. Bonder M.J. Deelen P. Zeng B. Kirsten H. Saha A. Kreuzhuber R. Yazar S. Brugge H. Oelen R. de Vries D.H. van der Wijst M.G.P. Kasela S. Pervjakova N. Alves I. Favé M.J. Agbessi M. Christiansen M.W. Jansen R. Seppälä I. Tong L. Teumer A. Schramm K. Hemani G. Verlouw J. Yaghootkar H. Sönmez Flitman R. Brown A. Kukushkina V. Kalnapenkis A. Rüeger S. Porcu E. Kronberg J. Kettunen J. Lee B. Zhang F. Qi T. Hernandez J.A. Arindrarto W. Beutner F. ‘t Hoen, P.A.C.; van Meurs, J.; van Dongen, J.; van Iterson, M.; Swertz, M.A.; Jan Bonder, M.; Dmitrieva, J.; Elansary, M.; Fairfax, B.P.; Georges, M.; Heijmans, B.T.; Hewitt, A.W.; Kähönen, M.; Kim, Y.; Knight, J.C.; Kovacs, P.; Krohn, K.; Li, S.; Loeffler, M.; Marigorta, U.M.; Mei, H.; Momozawa, Y.; Müller-Nurasyid, M.; Nauck, M.; Nivard, M.G.; Penninx, B.W.J.H.; Pritchard, J.K.; Raitakari, O.T.; Rotzschke, O.; Slagboom, E.P.; Stehouwer, C.D.A.; Stumvoll, M.; Sullivan, P.; ’t Hoen, P.A.C.; Thiery, J.; Tönjes, A.; van Dongen, J.; van Iterson, M.; Veldink, J.H.; Völker, U.; Warmerdam, R.; Wijmenga, C.; Swertz, M.; Andiappan, A.; Montgomery, G.W.; Ripatti, S.; Perola, M.; Kutalik, Z.; Dermitzakis, E.; Bergmann, S.; Frayling, T.; van Meurs, J.; Prokisch, H.; Ahsan, H.; Pierce, B.L.; Lehtimäki, T.; Boomsma, D.I.; Psaty, B.M.; Gharib, S.A.; Awadalla, P.; Milani, L.; Ouwehand, W.H.; Downes, K.; Stegle, O.; Battle, A.; Visscher, P.M.; Yang, J.; Scholz, M.; Powell, J.; Gibson, G.; Esko, T.; Franke, L. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression. Nat. Genet. 2021 53 9 1300 1310 10.1038/s41588‑021‑00913‑z 34475573
    [Google Scholar]
  23. Sun B.B. Chiou J. Traylor M. Benner C. Hsu Y.H. Richardson T.G. Surendran P. Mahajan A. Robins C. Vasquez-Grinnell S.G. Hou L. Kvikstad E.M. Burren O.S. Davitte J. Ferber K.L. Gillies C.E. Hedman Å.K. Hu S. Lin T. Mikkilineni R. Pendergrass R.K. Pickering C. Prins B. Baird D. Chen C.Y. Ward L.D. Deaton A.M. Welsh S. Willis C.M. Lehner N. Arnold M. Wörheide M.A. Suhre K. Kastenmüller G. Sethi A. Cule M. Raj A. Kang H.M. Burkitt-Gray L. Melamud E. Black M.H. Fauman E.B. Howson J.M.M. Kang H.M. McCarthy M.I. Nioi P. Petrovski S. Scott R.A. Smith E.N. Szalma S. Waterworth D.M. Mitnaul L.J. Szustakowski J.D. Gibson B.W. Miller M.R. Whelan C.D. Plasma proteomic associations with genetics and health in the UK Biobank. Nature 2023 622 7982 329 338 10.1038/s41586‑023‑06592‑6 37794186
    [Google Scholar]
  24. Kurki M.I. Karjalainen J. Palta P. Sipilä T.P. Kristiansson K. Donner K.M. Reeve M.P. Laivuori H. Aavikko M. Kaunisto M.A. Loukola A. Lahtela E. Mattsson H. Laiho P. Della Briotta Parolo P. Lehisto A.A. Kanai M. Mars N. Rämö J. Kiiskinen T. Heyne H.O. Veerapen K. Rüeger S. Lemmelä S. Zhou W. Ruotsalainen S. Pärn K. Hiekkalinna T. Koskelainen S. Paajanen T. Llorens V. Gracia-Tabuenca J. Siirtola H. Reis K. Elnahas A.G. Sun B. Foley C.N. Aalto-Setälä K. Alasoo K. Arvas M. Auro K. Biswas S. Bizaki-Vallaskangas A. Carpen O. Chen C.Y. Dada O.A. Ding Z. Ehm M.G. Eklund K. Färkkilä M. Finucane H. Ganna A. Ghazal A. Graham R.R. Green E.M. Hakanen A. Hautalahti M. Hedman Å.K. Hiltunen M. Hinttala R. Hovatta I. Hu X. Huertas-Vazquez A. Huilaja L. Hunkapiller J. Jacob H. Jensen J.N. Joensuu H. John S. Julkunen V. Jung M. Junttila J. Kaarniranta K. Kähönen M. Kajanne R. Kallio L. Kälviäinen R. Kaprio J. Kerimov N. Kettunen J. Kilpeläinen E. Kilpi T. Klinger K. Kosma V.M. Kuopio T. Kurra V. Laisk T. Laukkanen J. Lawless N. Liu A. Longerich S. Mägi R. Mäkelä J. Mäkitie A. Malarstig A. Mannermaa A. Maranville J. Matakidou A. Meretoja T. Mozaffari S.V. Niemi M.E.K. Niemi M. Niiranen T. O’Donnell C.J. Obeidat M. Okafo G. Ollila H.M. Palomäki A. Palotie T. Partanen J. Paul D.S. Pelkonen M. Pendergrass R.K. Petrovski S. Pitkäranta A. Platt A. Pulford D. Punkka E. Pussinen P. Raghavan N. Rahimov F. Rajpal D. Renaud N.A. Riley-Gillis B. Rodosthenous R. Saarentaus E. Salminen A. Salminen E. Salomaa V. Schleutker J. Serpi R. Shen H. Siegel R. Silander K. Siltanen S. Soini S. Soininen H. Sul J.H. Tachmazidou I. Tasanen K. Tienari P. Toppila-Salmi S. Tukiainen T. Tuomi T. Turunen J.A. Ulirsch J.C. Vaura F. Virolainen P. Waring J. Waterworth D. Yang R. Nelis M. Reigo A. Metspalu A. Milani L. Esko T. Fox C. Havulinna A.S. Perola M. Ripatti S. Jalanko A. Laitinen T. Mäkelä T.P. Plenge R. McCarthy M. Runz H. Daly M.J. Palotie A. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature 2023 613 7944 508 518 10.1038/s41586‑022‑05473‑8 36653562
    [Google Scholar]
  25. Orrù V. Steri M. Sidore C. Marongiu M. Serra V. Olla S. Sole G. Lai S. Dei M. Mulas A. Virdis F. Piras M.G. Lobina M. Marongiu M. Pitzalis M. Deidda F. Loizedda A. Onano S. Zoledziewska M. Sawcer S. Devoto M. Gorospe M. Abecasis G.R. Floris M. Pala M. Schlessinger D. Fiorillo E. Cucca F. Complex genetic signatures in immune cells underlie autoimmunity and inform therapy. Nat. Genet. 2020 52 10 1036 1045 10.1038/s41588‑020‑0684‑4 32929287
    [Google Scholar]
  26. Bowden J. Del Greco M. F.; Minelli, C.; Davey Smith, G.; Sheehan, N.A.; Thompson, J.R. Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: The role of the I2 statistic. Int. J. Epidemiol. 2016 45 6 dyw220 10.1093/ije/dyw220 27616674
    [Google Scholar]
  27. Burgess S. Labrecque J.A. Mendelian randomization with a binary exposure variable: Interpretation and presentation of causal estimates. Eur. J. Epidemiol. 2018 33 10 947 952 10.1007/s10654‑018‑0424‑6 30039250
    [Google Scholar]
  28. Burgess S. Thompson S.G. Avoiding bias from weak instruments in Mendelian randomization studies. Int. J. Epidemiol. 2011 40 3 755 764 10.1093/ije/dyr036 21414999
    [Google Scholar]
  29. Liu Z. Peng Z. Lin H. Zhou K. Liang L. Cao J. Huang Z. Mei J. Identifying potential drug targets for idiopathic pulmonary fibrosis: A mendelian randomization study based on the druggable genes. Respir. Res. 2024 25 1 217 10.1186/s12931‑024‑02848‑5 38783236
    [Google Scholar]
  30. Zhou J. Xu Y. Wang H. Chen C. Wang K. CDC42: Unlocking a novel therapeutic target for primary sclerosing cholangitis through Mendelian randomization. Am. J. Transl. Res. 2025 17 2 1076 1086 10.62347/BTYN8678 40092126
    [Google Scholar]
  31. Liu Y. Chen L. Hao W. Zhao K. Li C. Causal association between type 1 diabetes and autoimmune cholestasis: A bi-directional Mendelian randomized study. Int. J. Immunopathol. Pharmacol. 2025 39 03946320251327621 10.1177/03946320251327621 40216386
    [Google Scholar]
  32. Shu Y. Yang B. Liu X. Xu M. Deng C. Wu H. Causal effects from inflammatory bowel disease on liver function and disease: A two-sample Mendelian randomization study. Front. Med. 2024 10 1320842 10.3389/fmed.2023.1320842 38298515
    [Google Scholar]
  33. Burgess S. Butterworth A. Thompson S.G. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet. Epidemiol. 2013 37 7 658 665 10.1002/gepi.21758 24114802
    [Google Scholar]
  34. Burgess S. Thompson S.G. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur. J. Epidemiol. 2017 32 5 377 389 10.1007/s10654‑017‑0255‑x 28527048
    [Google Scholar]
  35. Bowden J. Davey Smith G. Haycock P.C. Burgess S. Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator. Genet. Epidemiol. 2016 40 4 304 314 10.1002/gepi.21965 27061298
    [Google Scholar]
  36. Hartwig F.P. Davey Smith G. Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int. J. Epidemiol. 2017 46 6 1985 1998 10.1093/ije/dyx102 29040600
    [Google Scholar]
  37. Cheung A. LaRusso N. Gores G. Lazaridis K. Epigenetics in the primary biliary cholangitis and primary sclerosing cholangitis. Semin. Liver Dis. 2017 37 2 159 174 10.1055/s‑0037‑1603324 28564724
    [Google Scholar]
  38. Moore R.M. Sun Z. Juran B.D. Lazaridis K.N. Genome-wide resolution peripheral blood methylome profiling reveals signatures for cholestatic liver disease. Epigenomics 2020 12 16 1363 1375 10.2217/epi‑2020‑0048 32914644
    [Google Scholar]
  39. Carter A.R. Sanderson E. Hammerton G. Richmond R.C. Davey Smith G. Heron J. Taylor A.E. Davies N.M. Howe L.D. Mendelian randomisation for mediation analysis: Current methods and challenges for implementation. Eur. J. Epidemiol. 2021 36 5 465 478 10.1007/s10654‑021‑00757‑1 33961203
    [Google Scholar]
  40. Zhang J. Hu Y. Xu J. Shao H. Zhu Q. Si H. Genetically predicted immune cells mediate the association between gut microbiota and autoimmune liver diseases. Front. Microbiol. 2024 15 1442506 10.3389/fmicb.2024.1442506 39736991
    [Google Scholar]
  41. Bowden J. Hemani G. Davey Smith G. Invited commentary: Detecting individual and global horizontal pleiotropy in mendelian randomization—a job for the humble heterogeneity statistic? Am. J. Epidemiol. 2018 187 12 2681 2685 10.1093/aje/kwy185 30188969
    [Google Scholar]
  42. van Kippersluis H. Rietveld C.A. Pleiotropy-robust Mendelian randomization. Int. J. Epidemiol. 2018 47 4 1279 1288 10.1093/ije/dyx002 28338774
    [Google Scholar]
  43. Chen L. Yang H. Li H. He C. Yang L. Lv G. Insights into modifiable risk factors of cholelithiasis: A Mendelian randomization study. Hepatology 2022 75 4 785 796 10.1002/hep.32183 34624136
    [Google Scholar]
  44. Hong J. Qu Z. Ji X. Li C. Zhang G. Jin C. Wang J. Zhang Y. Shen Y. Meng J. Zhou C. Fang C. Wang W. Yan S. Genetic associations between il-6 and the development of autoimmune arthritis are gender-specific. Front. Immunol. 2021 12 707617 10.3389/fimmu.2021.707617 34539640
    [Google Scholar]
  45. Burgess S. Sample size and power calculations in Mendelian randomization with a single instrumental variable and a binary outcome. Int. J. Epidemiol. 2014 43 3 922 929 10.1093/ije/dyu005 24608958
    [Google Scholar]
  46. Broadbent J.R. Foley C.N. Grant A.J. Mason A.M. Staley J.R. Burgess S. MendelianRandomization v0.5.0: Updates to an R package for performing Mendelian randomization analyses using summarized data. Wellcome Open Res. 2020 5 252 10.12688/wellcomeopenres.16374.2 33381656
    [Google Scholar]
  47. Afrache H. Gouret P. Ainouche S. Pontarotti P. Olive D. The butyrophilin (BTN) gene family: From milk fat to the regulation of the immune response. Immunogenetics 2012 64 11 781 794 10.1007/s00251‑012‑0619‑z 23000944
    [Google Scholar]
  48. Afrache H. Pontarotti P. Abi-Rached L. Olive D. Evolutionary and polymorphism analyses reveal the central role of BTN3A2 in the concerted evolution of the BTN3 gene family. Immunogenetics 2017 69 6 379 390 10.1007/s00251‑017‑0980‑z 28382515
    [Google Scholar]
  49. Arnett H.A. Viney J.L. Immune modulation by butyrophilins. Nat. Rev. Immunol. 2014 14 8 559 569 10.1038/nri3715 25060581
    [Google Scholar]
  50. Yamashiro H. Yoshizaki S. Tadaki T. Egawa K. Seo N. Stimulation of human butyrophilin 3 molecules results in negative regulation of cellular immunity. J. Leukoc. Biol. 2010 88 4 757 767 10.1189/jlb.0309156 20610803
    [Google Scholar]
  51. Ren H. Li S. Liu X. Li W. Hao J. Zhao N. Multi-omics analysis of the expression and prognostic value of the butyrophilins in breast cancer. J. Leukoc. Biol. 2021 110 6 1181 1195 10.1002/JLB.5MA0321‑158RR 34411352
    [Google Scholar]
  52. Lin Y. Zhou H. Li S. BTN3A2 expression is connected with favorable prognosis and high infiltrating immune in lung adenocarcinoma. Front. Genet. 2022 13 848476 10.3389/fgene.2022.848476 35873496
    [Google Scholar]
  53. Xu L. Yu D. Xu M. Liu Y. Yang L.X. Zou Q.C. Feng X.L. Li M.H. Sheng N. Yao Y.G. Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2. EBioMedicine 2024 107 105281 10.1016/j.ebiom.2024.105281 39142074
    [Google Scholar]
  54. Sarcognato S. Sacchi D. Grillo F. Cazzagon N. Fabris L. Cadamuro M. Cataldo I. Covelli C. Mangia A. Guido M. Autoimmune biliary diseases: Primary biliary cholangitis and primary sclerosing cholangitis. Pathologica 2021 113 3 170 184 10.32074/1591‑951X‑245 34294935
    [Google Scholar]
  55. Yan C. Koda S. Wu J. Zhang B.B. Yu Q. Netea M.G. Tang R.X. Zheng K.Y. Roles of trained immunity in the pathogenesis of cholangiopathies: A therapeutic target. Hepatology 2020 72 5 1838 1850 10.1002/hep.31395 32463941
    [Google Scholar]
  56. Zhu Y. Gao W. Zheng J. Bai Y. Tian X. Huang T. Lu Z. Dong D. Zhang A. Guo C. Huang Z. Phosphoantigen-induced inside-out stabilization of butyrophilin receptor complexes drives dimerization-dependent γδ TCR activation. Immunity 2025 58 7 1646 1659.e5 10.1016/j.immuni.2025.04.012 40334665
    [Google Scholar]
  57. Karunakaran M.M. Subramanian H. Jin Y. Mohammed F. Kimmel B. Juraske C. Starick L. Nöhren A. Länder N. Willcox C.R. Singh R. Schamel W.W. Nikolaev V.O. Kunzmann V. Wiemer A.J. Willcox B.E. Herrmann T. A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing. Nat. Commun. 2023 14 1 7617 10.1038/s41467‑023‑41938‑8 37993425
    [Google Scholar]
  58. 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 5 1039 1044 10.1073/pnas.1701237115 29339503
    [Google Scholar]
  59. Liu C. Yi S. Zhang M. Chen C.C. Liu Y. Zhang Z. Guo R.T. Yang Y. Molecular glue binding behavior of phosphoantigens to alpaca butyrophilins. J. Biol. Chem. 2025 301 6 108555 10.1016/j.jbc.2025.108555 40294650
    [Google Scholar]
  60. Chazaud B. Sonnet C. Lafuste P. Bassez G. Rimaniol A.C. Poron F. Authier F.J. Dreyfus P.A. Gherardi R.K. Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth. J. Cell Biol. 2003 163 5 1133 1143 10.1083/jcb.200212046 14662751
    [Google Scholar]
  61. Chazaud B. Brigitte M. Yacoub-Youssef H. Arnold L. Gherardi R. Sonnet C. Lafuste P. Chretien F. Dual and beneficial roles of macrophages during skeletal muscle regeneration. Exerc. Sport Sci. Rev. 2009 37 1 18 22 10.1097/JES.0b013e318190ebdb 19098520
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266423650251031072305
Loading
DNA Methylation-mediated BTN3A2 Regulation via CD14+CD16+ Monocytes Protects Against Primary Sclerosing Cholangitis
Bentham Science Publishers ; https://doi.org/10.2174/0115680266423650251031072305
/content/journals/ctmc/10.2174/0115680266423650251031072305
/content/journals/ctmc/10.2174/0115680266423650251031072305
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: BTN3 ; Causal relationship ; Immune cells ; cis-QTL ; Hepatology ; Single nucleotide polymorphism

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test