…
…
…
…
IL-4
…
IL-13
…
IL-13Rα1
…
γc
…
…

  1. Lieu R, Antonysamy S, Druzina Z, et al. Rapid and robust antibody Fab fragment crystallization utilizing edge-to-edge beta-sheet packing. PLoS One. 2020;15(9):e0232311. doi:10.1371/journal.pone.0232311. PDB: 6WGL, 6WGB.
  2. Hage T, Sebald W, Reinemer P. Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface. Cell. 1999;97(2):271-281. doi:10.1016/s0092-8674(00)80736-9. PDB: 1IAR.
  3. LaPorte SL, Juo ZS, Vaclavikova J, et al. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell. 2008;132(2):259-272. doi:10.1016/j.cell.2007.12.030. PDB: 3BPL, 3BPN, 3BPO.
  4. Junttila IS. Tuning the cytokine responses: an update on interleukin (IL)-4 and IL-13 receptor complexes. Front Immunol. 2018;9:888. doi:10.3389/fimmu.2018.00888.
  5. Junttila IS, Mizukami K, Dickensheets H, et al. Tuning sensitivity to IL-4 and IL-13: differential expression of IL-4Rα, IL-13Rα1, and γc regulates relative cytokine sensitivity. J Exp Med. 2008;205(11):2595-2608. doi:10.1084/jem.20080452.
  6. Ryan JJ, McReynolds LJ, Keegan A, et al. Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor. Immunity. 1996;4(2):123-132. doi:10.1016/s1074-7613(00)80677-9.
  7. Gandhi NA, Bennett BL, Graham NM, et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50. doi:10.1038/nrd4624.
  8. Le Floc'h A, Allinne J, Nagashima K, et al. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflammation. Allergy. 2020;75(5):1188-1204. doi:10.1111/all.14151.
  9. Harb H, Chatila TA. Mechanisms of dupilumab. Clin Exp Allergy. 2020;50(1):5-14. doi:10.1111/cea.13491.
  10. Li Z, Radin A, Li M, et al. Pharmacokinetics, pharmacodynamics, safety, and tolerability of dupilumab in healthy adult subjects. Clin Pharmacol Drug Dev. 2020;9(6):742-755. doi:10.1002/cpdd.798.
  11. UniProt Consortium. Interleukin-4 receptor subunit alpha, UniProtKB P24394; IL-13Rα1, P78552; γc, P31785.
  12. DUPIXENT (dupilumab) Prescribing Information, Regeneron Pharmaceuticals / Sanofi, sections 11, 12.1, 12.2. DailyMed, U.S. National Library of Medicine. EU: EMA, Dupixent EPAR (26/09/2017).
  13. Berman HM, Westbrook J, Feng Z, et al. The Protein Data Bank. Nucleic Acids Res. 2000;28(1):235-242. doi:10.1093/nar/28.1.235. RCSB PDB.
  14. Kabsch W. A solution for the best rotation to relate two sets of vectors. Acta Crystallogr A. 1976;32(5):922-923. doi:10.1107/S0567739476001873.
  15. Horn BKP. Closed-form solution of absolute orientation using unit quaternions. J Opt Soc Am A. 1987;4(4):629-642. doi:10.1364/JOSAA.4.000629.
  16. Rego N, Koes D. 3Dmol.js: molecular visualization with WebGL. Bioinformatics. 2015;31(8):1322-1324. doi:10.1093/bioinformatics/btu829.