IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response after severe trauma: A reverse translation study from a human cohort to a mouse trauma model

1. NCIPC. Web-based Injury Statistics Query and Reporting System. Centers for Disease Control and Prevention. 2014; https://www.cdc.gov/injury/wisqars/index.html.

2. Hall MJ, DeFrances CJ, Williams SN, Golosinskiy A, Schwartzman A. National Hospital Discharge Survey: 2007 summary. Natl Health Stat Report. 2010;(29):1–20, 24. 21086860

3. Gentile LF, Cuenca AG, Efron PA, Ang D, Bihorac A, McKinley BA, et al. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care. J Trauma Acute Care Surg. 2012; 72(6): 1491–1501. doi: 10.1097/TA.0b013e318256e000 22695412

4. Vanzant EL, Lopez CM, Ozrazgat-Baslanti T, Ungaro R, Davis R, Cuenca AG, et al. Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma. J Trauma Acute Care Surg. 2014; 76(1): 21–29. doi: 10.1097/TA.0b013e3182ab1ab5 24368353

5. Regel G, Grotz M, Weltner T, Sturm JA, Tscherne H. Pattern of organ failure following severe trauma. World J Surg. 1996; 20(4): 422–429. 8662130

6. Schlag G, Redl H, Hallström S. The cell in shock: the origin of multiple organ failure. Resuscitation. 1991; 21(2–3): 137–180. 1650020

7. Namas RA, Vodovotz Y, Almahmoud K, Abdul-Malak O, Zaaqoq A, Namas R, et al. Temporal patterns of circulating inflammation biomarker networks differentiate susceptibility to nosocomial infection following blunt trauma in humans. Ann Surg. 2016; 263: 191–198. doi: 10.1097/SLA.0000000000001001 25371118

8. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A. 2013;110(9):3507–12. doi: 10.1073/pnas.1222878110 23401516

9. Efron PA, Mohr AM, Moore FA, Moldawer LL. The future of murine sepsis and trauma research models. J Leukoc Biol. 2015;98(6):945–52. doi: 10.1189/jlb.5MR0315-127R 26034205

10. Namas R, Mi Q, Namas R, Almahmoud K, Zaaqoq A, Abdul Malak O, et al. Insights into the role of chemokines, damage-associated molecular patterns, and lymphocyte-derived mediators from computational models of trauma-induced inflammation. Antioxid Redox Signaling. 2015; 10: 1370–1387.

11. Ware LB. Pathophysiology of acute lung injury and the acute respiratory distress syndrome. Semin Respir Crit Care Med. 2006; 27(4): 337–349. 16909368

12. Strieter RM, Belperio JA, Keane MP. Host innate defenses in the lung: the role of cytokines. Curr Opin Infect Dis. 2003; 16(3): 193–198. doi: 10.1097/01.qco.0000073766.11390.0e 12821807

13. Miller AC, Rashid RM, Elamin EM. The "T" in trauma: the helper T-cell response and the role of immunomodulation in trauma and burn patients. J Trauma. 2007; 63(6): 1407–1417. doi: 10.1097/TA.0b013e31815b839e 18212667

14. Gryglewski A, Majcher P, Szczepanik M. Immunological aspects of trauma. Postepy Hig Med Dosw (Online). 2006; 60: 192–200.

15. Iwasaka H, Noguchi T. Th1/Th2 balance in systemic inflammatory response syndrome (SIRS). Nihon Rinsho. 2004; 62(12): 2237–2243. 15597790

16. Wang DC. [Attach importance to research on lymph circulation system after burns]. Zhonghua Shao Shang Za Zhi. 2011; 27(1): 3–5. 21591331

17. Russ MA, Reith HB. The severity of infection induces a shift in the type 1/Type 2 T-helper cell balance in patients with or without peritonitis. Surg Infect (Larchmt). 2003; 4(3): 247–254.

18. Matta BM, Reichenbach DK, Blazar BR, Turnquist HR. Alarmins and their receptors as modulators and indicators of alloimmune responses. Am J Transplant. 2017; 17(2): 320–327. doi: 10.1111/ajt.13887 27232285

19. Klune JR, Dhupar R, Cardinal J, Billiar TR, Tsung A. HMGB1: endogenous danger signaling. Mol Med. 2008; 14(7–8): 476–484. doi: 10.2119/2008-00034.Klune 18431461

20. Hirsiger S, Simmen HP, Werner CM, Wanner GA, Rittirsch D. Danger signals activating the immune response after trauma. Mediators Inflamm. 2012; 2012: 315941. doi: 10.1155/2012/315941 22778496

21. Liew FY, Girard JP, Turnquist HR. Interleukin-33 in health and disease. Nat Rev Immune. 2016; 16(11): 676–689.

22. Saenz SA, Taylor BC, Artis D. Welcome to the neighborhood: epithelial cell-derived cytokines license innate and adaptive immune responses at mucosal sites. Immune Rev. 2008; 226: 172–190.

23. García-Miguel M, González MJ, Quera R, Hermoso MA. Innate immunity modulation by the IL-33/ST2 system in intestinal mucosa. Biomed Res Int. 2013; 2013:142492. doi: 10.1155/2013/142492 23484079

24. Walker JA, McKenzie AN. Development and function of group 2 innate lymphoid cells. Curr Opin Immunol. 2013; 25(2): 148–155. doi: 10.1016/j.coi.2013.02.010 23562755

25. Hammad H, Lambrecht BN. Barrier Epithelial Cells and the Control of Type 2 Immunity. Immunity. 2015; 43(1): 29–40. doi: 10.1016/j.immuni.2015.07.007 26200011

26. Mjösberg J, Eidsmo L. Update on innate lymphoid cells in atopic and non-atopic inflammation in the airways and skin. Clin Exp Allergy. 2014; 44(8): 1033–1043. doi: 10.1111/cea.12353 24912880

27. KleinJan A, Klein Wolterink RG, Levani Y, de Bruijn MJ, Hoogsteden HC, van Nimwegen M, et al. Enforced expression of Gata3 in T cells and group 2 innate lymphoid cells increases susceptibility to allergic airway inflammation in mice. J Immunol. 2014; 192(4): 1385–1394. doi: 10.4049/jimmunol.1301888 24415780

28. Duerr CU, Fritz JH. Regulation of group 2 innate lymphoid cells. Cytokine. 2016; 87: 1–8. doi: 10.1016/j.cyto.2016.01.018 27255596

29. Oboki K, Ohno T, Kajiwara N, Arae K, Morita H, Ishii A, et al. IL-33 is a crucial amplifier of innate rather than acquired immunity. Proc Natl Acad Sci U. S. A. 2010; 107(43), 18581–18586. doi: 10.1073/pnas.1003059107 20937871

30. Zhang Y, Zhang J, Korff S, Ayoob F, Vodovotz Y, Billiar TR. Delayed neutralization of interleukin 6 reduces organ injury, selectively suppresses inflammatory mediator, and partially normalizes immune dysfunction following trauma and hemorrhagic shock. Shock. 2014; 42(3): 218–227. doi: 10.1097/SHK.0000000000000211 24978887

31. Cai C, Cao Z, Loughran PA, Kim S, Darwiche S, Korff S, et al. Mast cells play a critical role in the systemic inflammatory response and end-organ injury resulting from trauma. J Am Coll Surg. 2011; 213(5): 604–615. doi: 10.1016/j.jamcollsurg.2011.08.009 21920785

32. Edmonds RD, Vodovotz Y, Lagoa C, Dutta-Moscato J, Yang Y, Fink MP, et al. Transcriptomic response of murine liver to severe injury and hemorrhagic shock: a dual-platform microarray analysis. Physiol Genomics. 2011; 43(20):1170–83. doi: 10.1152/physiolgenomics.00020.2011 21828244

33. Pfeifer R, Kobbe P, Darwiche SS, Billiar TR, Pape HC. The Role of Hemorrhage in the Induction of Systemic Inflammation and Remote Organ Damage: Analysis of Combined Pseudo-Fracture and Hemorrhagic Shock. J Orthop Res. 2011; 29: 270–4. doi: 10.1002/jor.21214 20690183

34. Halim TY, Takei F. Isolation and characterization of mouse innate lymphoid cells. Curr Protoc Immunol. 2014; 106: 3.25.1–13.

35. Halim TY, MacLaren A, Romanish MT, Gold MJ, McNagny KM, Takei F. Retinoic-acid-receptor-related orphan nuclear receptor alpha is required for natural helper cell development and allergic inflammation. Immunity. 2012; 37(3): 463–474. doi: 10.1016/j.immuni.2012.06.012 22981535

36. Swamydas M, Luo Y, Dorf ME, Lionakis MS. Isolation of mouse neutrophils. Curr Protoc Immunol. 2015; 110: 3.20.1–3.20.15.

37. Bueno M, Lai Y-C, Romero Y, Brands J, StCroix C, Kamga C, et al. PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis. J Clin Invest. 2015; 125 (2): 521–538. doi: 10.1172/JCI74942 25562319

38. Dryad Digital Repository. Durham (NC): Dryad. [cited 2017 Jul 10]. http://dx.doi.org/10.5061/dryad.kt8m4.

39. Ma J, Guo W, Li Z, Wang B, Li S, Wang P. Hip Osteonecrosis Is Associated with Increased Plasma IL-33 Level. Mediators Inflamm. 2017;2017:1732638. doi: 10.1155/2017/1732638 28167850

40. Voloshyna I, Mucci T, Sher J, Fonacier LS, Littlefield MJ, Carsons S, et al. Plasma IL-33 in atopic patients correlates with pro-inflammatory cytokines and changes cholesterol transport protein expression: a surprising neutral overall impact on atherogenicity. Clin Exp Allergy. 2015;45(10):1554–65. doi: 10.1111/cea.12516 25703059

41. Barbosa IG, Morato IB, de Miranda AS, Bauer ME, Soares JC, Teixeira AL. A preliminary report of increased plasma levels of IL-33 in bipolar disorder: further evidence of pro-inflammatory status. J Affect Disord. 2014;157:41–4. doi: 10.1016/j.jad.2013.12.042 24581826

42. Sun M, Ma HF, Che YY, Cui X. Reduced IL-33 plasma levels in aplastic anemia. Cancer Cell Int. 2015;15:118. doi: 10.1186/s12935-015-0270-5 26677348

43. Mitsui A, Tada Y, Takahashi T, Shibata S, Kamata M, Miyagaki T, et al. Serum IL-33 levels are increased in patients with psoriasis. Clin Exp Dermatol. 2016;41(2):183–9. doi: 10.1111/ced.12670 25976154

44. Hayakawa H, Hayakawa M, Kume A, Tominaga S. Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation. J Biol Chem. 2007;282(36):26369–26380. doi: 10.1074/jbc.M704916200 17623648

45. Mueller T, Jaffe AS. Soluble ST2—analytical considerations. Am J Cardiol. 2015; 115(7 Suppl), 8B–21B. doi: 10.1016/j.amjcard.2015.01.035 25697919

46. Díaz-Jiménez D, De la Fuente M, Dubois-Camacho K, Landskron G, Fuentes J, Pérez T, et al. Soluble ST2 is a sensitive clinical marker of ulcerative colitis evolution. BMC Gastroenterol. 2016;26(16):103.

47. Chaudry IH, Ayala A. Mechanism of increased susceptibility to infection following hemorrhage. Am J Surg. 1993;165(2A Suppl):59S–67S. 8439001

48. Marik PE, Flemmer M. The immune response to surgery and trauma: Implications for treatment. J Trauma Acute Care Surg. 2012;73(4):801–808. doi: 10.1097/TA.0b013e318265cf87 22976420

49. Volpin G, Cohen M, Assaf M, Meir T, Katz R, Pollack S. Cytokine levels (IL-4, IL-6, IL-8 and TGFβ) as potential biomarkers of systemic inflammatory response in trauma patients. Int Orthop. 2014;38(6):1303–1309. doi: 10.1007/s00264-013-2261-2 24402554

50. Balvers K, Curry N, Kleinveld DJ, Böing AN, Nieuwland R, Goslings JC, et al. Endogenous microparticles drive the proinflammatory host immune response in severely injured trauma patients. Shock. 2015;43(4):317–321. doi: 10.1097/SHK.0000000000000321 25565646

51. Kohut LK, Darwiche SS, Brumfield JM, Frank AM, Billiar TR. Fixed volume or fixed pressure: a murine model of hemorrhagic shock. J Vis Exp. 2011;6(52). pii: 2068.

52. Darwiche SS, Kobbe P, Pfeifer R, Kohut L, Pape HC, Billiar T. Pseudofracture: an acute peripheral tissue trauma model. J Vis Exp. 2011;18(50):2074.

53. Korff S, Loughran P, Cai C, Lee YS, Scott M, Billiar TR. Eritoran attenuates tissue damage and inflammation in hemorrhagic shock/trauma. J Surg Res. 2013; 184(2):e17–25. doi: 10.1016/j.jss.2013.03.023 23777984

54. Büttner C, Lun A, Splettstoesser T, Kunkel G, Renz H. Monoclonal anti-interleukin-5 treatment suppresses eosinophil but not T-cell functions. Eur Respir J. 2003;21(5):799–803. 12765424

55. Ather JL, Foley KL, Suratt BT, Boyson JE, Poynter ME. Airway epithelial NF-κB activation promotes the ability to overcome inhalational antigen tolerance. Clin Exp Allergy. 2015;45(7):1245–58. doi: 10.1111/cea.12491 25616105

56. McSorley HJ, Blair NF, Smith KA, McKenzie AN, Maizels RM. Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth secreted products in airway allergy. Mucosal Immunol. 2014;7(5):1068–78. doi: 10.1038/mi.2013.123 24496315

57. Koscsó B, Trepakov A, Csóka B, Németh ZH, Pacher P, Eltzschig HK, et al. Stimulation of A2B adenosine receptors protects against trauma-hemorrhagic shock-induced lung injury. Purinergic Signal. 2013;9(3):427–432. doi: 10.1007/s11302-013-9362-7 23584760

58. Liu FC, Zheng CW, Yu HP. Maraviroc-Mediated Lung Protection following Trauma-Hemorrhagic Shock. Biomed Res Int. 2016;2016:5302069. doi: 10.1155/2016/5302069 27556035

59. Nussbaum JC, Van Dyken SJ, Moltke von J, Cheng LE, Mohapatra A, Molofsky AB, et al. Type 2 innate lymphoid cells control eosinophil homeostasis. Nature. 2013; 502(7470):245–248. doi: 10.1038/nature12526 24037376

60. Molofsky AB, Van Gool F, Liang HE, Van Dyken SJ, Nussbaum JC, Lee J, et al. Interleukin-33 and Interferon-γ Counter-Regulate Group 2 Innate Lymphoid Cell Activation during Immune Perturbation. Immunity. 2015;43(1):161–74. doi: 10.1016/j.immuni.2015.05.019 26092469

61. Bartemes KR, Kephart GM, Fox SJ, Kita H. Enhanced innate type 2 immune response in peripheral blood from patients with asthma. J Allergy Clin Immunol. 2014;134(3):671–678. doi: 10.1016/j.jaci.2014.06.024 25171868

62. Cui W, Zhang P, Gu J, Tian Y, Gao X, Liu Y, et al. Vitamin A Deficiency Promotes Inflammation by Induction of Type 2 Cytokines in Experimental Ovalbumin-Induced Asthma Murine Model. Inflammation. 2016;39(5):1798–1804. doi: 10.1007/s10753-016-0415-2 27525423

63. Bunt SK, Clements VK, Hanson EM, Sinha P, Ostrand-Rosenberg S. Inflammation enhances myeloid-derived suppressor cell cross-talk by signaling through Toll-like receptor 4. J Leukoc Biol. 2009;85(6):996–1004. doi: 10.1189/jlb.0708446 19261929

64. Sinha P, Clements V K, Bunt S K, Albelda S M, Ostrand-Rosenberg S. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol. 2007;179:977–983. 17617589

65. Song GY, Chung CS, Chaudry IH, Ayala A. Immune suppression in polymicrobial sepsis: differential regulation of Th1 and Th2 responses by p38 MAPK. J Surg Res. 2000;91(2):141–6. doi: 10.1006/jsre.2000.5928 10839963

66. Bryk JA, Popovic PJ, Zenati MS, Munera V, Pribis JP, Ochoa JB. Nature of myeloid cells expressing arginase 1 in peripheral blood after trauma. J Trauma. 2010;68(4):843–852. doi: 10.1097/TA.0b013e3181b026e4 19996805

67. Makarenkova VP, Bansal V, Matta BM, Perez LA, Ochoa JB. CD11b+/Gr-1+ myeloid suppressor cells cause T cell dysfunction after traumatic stress. J Immune. 2006;176:2085–2094.

68. Klein Wolterink RG, Kleinjan A, van Nimwegen M, Bergen I, de Bruijn M, Levani Y, et al. Pulmonary innate lymphoid cells are major producers of IL-5 and IL-13 in murine models of allergic asthma. Eur J Immunol. 2012;42(5):1106–16. doi: 10.1002/eji.201142018 22539286

69. Huang Y, Guo L, Qiu J, Chen X, Hu-Li J, Siebenlist U, et al. IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential 'inflammatory' type 2 innate lymphoid cells. Nat Immunol. 2015;16(2):161–169. doi: 10.1038/ni.3078 25531830

70. Kapp A, Zeck-Kapp G. Activation of the oxidative metabolism in human polymorphonuclear neutrophilic granulocytes: the role of immuno-modulating cytokines. J Invest Dermatol. 1990;95(6 Suppl):94S–99S. 2258641

71. Kapp A, Zeck-Kapp G. Interleukin-5-induced granulocyte activation in atopic patients. Br J Dermatol. 1991;125(2):108–115. 1911293

72. Zarbock A, Allegretti M, Ley K. Therapeutic inhibition of CXCR2 by Reparixin attenuates acute lung injury in mice. Br J Pharmacol. 2008;155(3):357–364. doi: 10.1038/bjp.2008.270 18587419

73. Schuh JM, Blease K, Hogaboam CM. CXCR2 is necessary for the development and persistence of chronic fungal asthma in mice. J Immunol. 2002;168(3):1447–1456. 11801688

74. Mizutani N, Nabe T, Yoshino S. IL-17A promotes the exacerbation of IL-33-induced airway hyperresponsiveness by enhancing neutrophilic inflammation via CXCR2 signaling in mice. J Immunol. 2014;192(4):1372–1384. doi: 10.4049/jimmunol.1301538 24446518