Role of the IL-33-ST2 axis in sepsis

Hui Xu; Heth R. Turnquist; Rosemary Hoffman; Timothy R. Billiar

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Role of the IL-33-ST2 axis in sepsis

REVIEW | Updated：2022-12-27

- Role of the IL-33-ST2 axis in sepsis
- Military Medical Research Vol. 4, Issue 1, Pages: 50-60(2017)
- Affiliations：
  
  1.Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
  2.State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  3.Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
- Author bio：
  
  *: billiartr@upmc.edu
- Funds：
- DOI：
  CLC：
- Published：2017-03
- Accepted：
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Hui Xu, Heth R. Turnquist, Rosemary Hoffman, et al. Role of the IL-33-ST2 axis in sepsis[J]. Military Medical Research, 2017, 4(1): 50-60.
DOI：

Hui Xu, Heth R. Turnquist, Rosemary Hoffman, et al. Role of the IL-33-ST2 axis in sepsis[J]. Military Medical Research, 2017, 4(1): 50-60. DOI：

摘要

Abstract

Sepsis remains a major clinical problem with high morbidity and mortality. As new inflammatory mediators are characterized

it is important to understand their roles in sepsis. Interleukin 33 (IL-33) is a recently described member of the IL-1 family that is widely expressed in cells of barrier tissues. Upon tissue damage

IL-33 is released as an alarmin and activates various types of cells of both the innate and adaptive immune system through binding to the ST2/IL-1 receptor accessory protein complex. IL-33 has apparent pleiotropic functions in many disease models

with its actions strongly shaped by the local microenvironment. Recent studies have established a role for the IL-33-ST2 axis in the initiation and perpetuation of inflammation during endotoxemia

but its roles in sepsis appear to be organism and model dependent. In this review

we focus on the recent advances in understanding the role of the IL-33/ST2 axis in sepsis.

关键词

Keywords

references

Lakshmikanth CL , Jacob SP , Chaithra VH , de Castro-Faria-Neto HC , Marathe GK . Sepsis: in search of cure . Inflamm Res . 2016 ; 65 : 587 - 602 .

Liew FY , Pitman NI , McInnes IB . Disease-associated functions of IL-33: the new kid in the IL-1 family . Nat Rev Immunol . 2010 ; 10 : 103 - 10 .

Milovanovic M , Volarevic V , Radosavljevic G , Jovanovic I , Pejnovic N , Arsenijevic N , et al . IL-33/ST2 axis in inflammation and immunopathology . Immunol Res . 2012 ; 52 : 89 - 99 .

Kurowska-Stolarska M , Hueber A , Stolarski B , McInnes IB . Interleukin-33: a novel mediator with a role in distinct disease pathologies . J Intern Med . 2011 ; 269 : 29 - 35 .

Palmer G , Gabay C . Interleukin-33 biology with potential insights into human diseases . Nat Rev Rheumatol . 2011 ; 7 : 321 - 9 .

Singer M , Deutschman CS , Seymour CW , Shankar-Hari M , Annane D , Bauer M , et al . The third international consensus definitions for sepsis and septic shock (Sepsis-3) . JAMA . 2016 ; 315 : 801 - 10 .

Angus DC , van der Poll T . Severe sepsis and septic shock . N Engl J Med . 2013 ; 369 : 840 - 51 .

Wiersinga WJ , Leopold SJ , Cranendonk DR , van der Poll T . Host innate immune responses to sepsis . Virulence . 2014 ; 5 : 36 - 44 .

Gaieski DF , Edwards JM , Kallan MJ , Carr BG . Benchmarking the incidence and mortality of severe sepsis in the United States . Crit Care Med . 2013 ; 41 : 1167 - 74 .

Lagu T , Rothberg MB , Shieh MS , Pekow PS , Steingrub JS , Lindenauer PK . Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007 . Crit Care Med . 2012 ; 40 : 754 - 61 .

Kempker JA . Martin GS2. The changing epidemiology and definitions of sepsis . Clin Chest Med . 2016 ; 37 : 165 - 79 .

Cohen J , Vincent JL , Adhikari NK , Machado FR , Angus DC , Calandra T , et al . Sepsis: a roadmap for future research . Lancet Infect Dis . 2015 ; 15 : 581 - 614 .

Seeley EJ , Bernard GR . Therapeutic targets in sepsis: past, present, and future . Clin Chest Med . 2016 ; 37 : 181 - 9 .

Kaukonen KM , Bailey M , Suzuki S , Pilcher D , Bellomo R . Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012 . JAMA . 2014 ; 311 : 1308 - 16 .

Vincent JL , Marshall JC , Namendys-Silva SA , François B , Martin-Loeches I , Lipman J , et al . Assessment of the worldwide burden of critical illness: the intensive care over nations (ICON) audit . Lancet Respir Med . 2014 ; 2 : 380 - 6 .

Schulte W , Bernhagen J , Bucala R . Cytokines in sepsis: potent immunoregulators and potential therapeutic targets–an updated view . Mediators Inflamm . 2013 ; 2013 : 165974 .

Cohen J . The immunopathogenesis of sepsis . Nature . 2002 ; 420 : 885 - 91 .

Oberholzer A , Oberholzer C , Moldawer L . Sepsis syndromes: understanding the role of innate and acquired immunity . Shock . 2001 ; 16 : 83 - 96 .

Opal SM . New perspectives on immunomodulatory therapy for bacteraemia and sepsis . Int J Antimicrob Ag . 2010 ; 36 Suppl 2 : S70 - 3 .

van der Poll T , Opal SM . Host-pathogen interactions in sepsis . Lancet Infect Dis . 2008 ; 8 : 32 - 43 .

Kawai T , Akira S . The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors . Nat Immunol . 2010 ; 11 : 373 - 84 .

Opal SM . The host response to endotoxin, anti-LPS strategies and the management of severe sepsis . Int J Med Microbiol . 2007 ; 297 : 365 - 77 .

Stowe I , Lee B , Kayagaki N . Caspase-11: arming the guards against bacterial infection . Immunol Rev . 2015 ; 265 : 75 - 84 .

Akira S , Takeda K . Toll-like receptor signaling . Nat Rev Immunol . 2004 ; 4 : 499 - 511 .

O'Neill LA . A critical role for citrate metabolism in LPS signalling . Biochem J . 2011 ; 438 : 5 - 6 .

Opal SM , Huber CE . Bench-to-bedside review: Toll-like receptors and their role in septic shock . Crit Care . 2002 ; 6 : 1 - 12 .

Lakhani SA , Bogue CW . Toll-like receptor signaling in sepsis . Curr Opin Pediatr . 2003 ; 15 : 278 - 82 .

Ramnath RD , Weing S , He M , Sun J , Zhang H , Bara MS , et al . Inflammatory mediators in sepsis: cytokines, chemokines, adhesion molecules and gases . J Organ Dysfunct . 2009 ; 2 : 80 - 92 .

Hoesel LM , Neff TA , Neff SB , Younger JG , Olle EW , Gao H , et al . Harmful and protective roles of neutrophils in sepsis . Shock . 2005 ; 24 : 40 - 7 .

Laban-Guceva N , Bogoev M , Antova M . Serum concentrations of interleukin (IL-)1alpha, 1beta, 6 and tumor necrosis factor (TNF-) alpha in patients with thyroid eye disease (TED) . Med Arh . 2007 ; 61 : 203 - 6 .

Xu J , Jiang Y , Wang J , Shi X , Liu Q , Liu Z , et al . Macrophage endocytosis of high-mobility group box 1 triggers pyroptosis . Cell Death Differ . 2014 ; 21 : 1229 - 39 .

von Moltke J , Trinidad NJ , Moayeri M , Kintzer AF , Wang SB , van Rooijen N , et al . Rapid induction of inflammatory lipid mediators by the inflammasome in vivo . Nature . 2012 ; 490 : 107 - 11 .

Meng W , Paunel-Görgülü A , Flohé S , Hoffmann A , Witte I , MacKenzie C , et al . Depletion of neutrophil extracellular traps in vivo results in hypersusceptibility to polymicrobial sepsis in mice . Crit Care . 2012 ; 16 : R137 .

Weaver CT , Hatton RD , Mangan PR , Harrington LE . IL-17 family cytokines and the expanding diversity of effector T-cell lineages . Annu Rev Immunol . 2007 ; 25 : 821 - 52 .

Opal SM , DePalo VA . Anti-inflammatory cytokines . Chest . 2000 ; 117 : 1162 - 72 .

Rittirsch D , Flierl MA , Ward PA . Harmful molecular mechanisms in sepsis . Nat Rev Immunol . 2008 ; 8 : 776 - 87 .

Venet F , Chung CS , Monneret G , Huang X , Horner B , Garber M , et al . Regulatory T cell populations in sepsis and trauma . J Leukoc Biol . 2008 ; 83 : 523 - 35 .

Cuenca AG , Delano MJ , Kelly-Scumpia KM , Moreno C , Scumpia PO , Laface DM , et al . A paradoxical role for myeloid-derived suppressor cells in sepsis and trauma . Mol Med . 2011 ; 17 : 281 - 92 .

Hotchkiss RS , Nicholson DW . Apoptosis and caspases regulate death and inflammation in sepsis . Nat Rev Immunol . 2006 ; 6 : 813 - 22 .

Baekkevold ES , Roussigné M , Yamanaka T , Johansen FE , Jahnsen FL , Amalric F , et al . Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules . Am J Pathol . 2003 ; 163 : 69 - 79 .

Schmitz J , Owyang A , Oldham E , Song Y , Murphy E , McClanahan TK , et al . IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines . Immunity . 2005 ; 23 : 479 - 90 .

Sanada S , Hakuno D , Higgins LJ , Schreiter ER , McKenzie AN , Lee RT . IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system . J Clin Invest . 2007 ; 117 : 1538 - 49 .

Moussion C , Ortega N , Girard JP . The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo : a novel ‘alarmin’? PLoS One . 2008 ; 3 : e3331 .

Miller AM , Xu D , Asquith DL , Denby L , Li Y , Sattar N , et al . IL-33 reduces the development of atherosclerosis . J Exp Med . 2008 ; 205 : 339 - 46 .

Tjota MY , Williams JW , Lu T , Clay BS , Byrd T , Hrusch CL , et al . IL-33-dependent induction of allergic lung inflammation by FcgammaRIII signaling . J Clin Invest . 2013 ; 123 : 2287 - 97 .

Hardman CS , Panova V , McKenzie AN . IL-33 citrine reporter mice reveal the temporal and spatial expression of IL-33 during allergic lung inflammation . Eur J Immunol . 2013 ; 43 : 488 - 98 .

Cayrol C , Girard JP . IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy . Curr Opin Immunol . 2014 ; 31 : 31 - 7 .

Roussel L , Erard M , Cayrol C , Girard JP . Molecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A-H2B acidic pocket . EMBO Rep . 2008 ; 9 : 1006 - 12 .

Mirchandani AS , Salmond RJ , Liew FY . Interleukin-33 and the function of innate lymphoid cells . Trends Immunol . 2012 ; 33 : 389 - 96 .

Oboki K , Nakae S , Matsumoto K , Saito H . IL-33 and airway inflammation . Allergy, Asthma Immunol Res . 2011 ; 3 : 81 - 8 .

Pei C , Barbour M , Fairlie-Clarke KJ , Allan D , Mu R , Jiang HR . Emerging role of interleukin-33 in autoimmune diseases . Immunology . 2014 ; 141 : 9 - 17 .

Tominaga S . A putative protein of a growth specific cDNA from BALB/c-3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor . FEBS Lett . 1989 ; 258 : 301 - 4 .

Oshikawa K , Yanagisawa K , Tominaga S , Sugiyama Y . Expression and function of the ST2 gene in a murine model of allergic airway inflammation . Clin Exp Allergy . 2002 ; 32 : 1520 - 6 .

Oshikawa K , Kuroiwa K , Tago K , Iwahana H , Yanagisawa K , Ohno S , et al . Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation . Am J Respir Crit Care Med . 2001 ; 164 : 277 - 81 .

Kuroiwa K , Arai T , Okazaki H , Minota S , Tominaga S . Identification of human ST2 protein in the sera of patients with auto- immune diseases . Biochem Biophys Res Commun . 2001 ; 284 : 1104 - 8 .

Tajima S , Oshikawa K , Tominaga S , Sugiyama Y . The increase in serum soluble ST2 protein upon acute exacerbation of idiopathic pulmonary fibrosis . Chest . 2003 ; 124 : 1206 - 14 .

Weinberg EO , Shimpo M , Hurwitz S , Tominaga S , Rouleau JL , Lee RT . Identification of serum soluble ST2 receptor as a novel heart failure biomarker . Circulation . 2003 ; 107 : 721 - 6 .

Mathews LR , Lott JM , Isse K , Lesniak A , Landsittel D , Demetris AJ , et al . Elevated ST2 distinguishes incidences of pediatric heart and small bowel transplant rejection . Am J Transplant . 2016 ; 16 : 938 - 50 .

Seidelin JB , Rogler G , Nielsen OH . A role for interleukin-33 in TH2-polarized intestinal inflammation? Mucosal Immunol . 2011 ; 4 : 496 - 502 .

Aoki S , Hayakawa M , Ozaki H , Takezako N , Obata H , Ibaraki N , et al . ST2 gene expression is proliferation-dependent and its ligand, IL-33, induces inflammatory reaction in endothelial cells . Mol Cell Biochem . 2010 ; 335 : 75 - 81 .

Choi YS , Choi HJ , Min JK , Pyun BJ , Maeng YS , Park H , et al . Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production . Blood . 2009 ; 114 : 3117 - 26 .

Yagami A , Orihara K , Morita H , Futamura K , Hashimoto N , Matsumoto K , et al . IL-33 mediates inflammatory responses in human lung tissue cells . J Immunol . 2010 ; 185 : 5743 - 50 .

Funakoshi-Tago M , Tago K , Hayakawa M , Tominaga S , Ohshio T , Sonoda Y , et al . TRAF6 is a critical signal transducer in IL-33 signaling pathway . Cell Signal . 2008 ; 20 : 1679 - 86 .

Kurowska-Stolarska M , Kewin P , Murphy G , Russo RC , Stolarski B , Garcia CC , et al . IL-33 induces antigen-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4 . J Immunol . 2008 ; 181 : 4780 - 90 .

Villarreal DO , Wise MC , Walters JN , Reuschel E , Choi MJ , Obeng-Adjei N , et al . Alarmin IL-33 acts as an immunoadjuvant to enhance antigen-specific tumor immunity . Cancer Res . 2014 ; 74 : 1789 - 800 .

Villarreal DO , Weiner DB . Interleukin 33: a switch-hitting cytokine . Curr Opin Immunol . 2014 ; 28 : 102 - 6 .

Matta BM , Turnquist HR . Expansion of regulatory T cells in vitro and in vivo by IL-33 . Methods Mol Biol . 2016 ; 1371 : 29 - 41 .

Liew FY , Girard JP , Turnquist HR . Interleukin-33 in health and disease . Nat Rev Immunol . 2016 ; 16 : 676 - 89 .

Turnquist HR , Zhao Z , Rosborough BR , Liu Q , Castellaneta A , Isse K , et al . IL-33 expands suppressive CD11b + Gr-1(int) and regulatory T cells, including ST2L+Foxp3+ cells, and mediates regulatory T cell-dependent promotion of cardiac allograft survival . J Immunol . 2011 ; 187 : 4598 - 610 .

Matta BM , Reichenbach DK , Zhang X , Mathews L , Koehn BH , Dwyer GK , et al . Peri-alloHCT IL-33 administration expands recipient T-regulatory cells that protect mice against acute GVHD . Blood . 2016 ; 128 : 427 - 39 .

Kuswanto W , Burzyn D , Panduro M , Wang KK , Jang YC , Wagers AJ , et al . Poor repair of skeletal muscle in aging mice reflects a defect in local, interleukin-33-dependent accumulation of regulatory T cells . Immunity . 2016 ; 44 : 355 - 67 .

Noel G , Arshad MI , Filliol A , Genet V , Rauch M , Lucas-Clerc C , et al . Ablation of interaction between IL-33 and ST2+ regulatory T cells increases immune cell-mediated hepatitis and activated NK cell liver infiltration . Am J Physiol Gastrointest Liver Physiol . 2016 ; 311 : G313 - 23 .

Duan L , Chen J , Zhang H , Yang H , Zhu P , Xiong A , et al . Interleukin-33 ameliorates experimental colitis through promoting Th2/Foxp3+regulatory T-cell responses in mice . Mol Med . 2012 ; 18 : 753 - 61 .

Schiering C , Krausgruber T , Chomka A , Fröhlich A , Adelmann K , Wohlfert EA , et al . The alarmin IL-33 promotes regulatory T-cell function in the intestine . Nature . 2014 ; 513 : 564 - 8 .

Moulin D , Donzé O , Talabot-Ayer D , Mézin F , Palmer G , Gabay C . Interleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cells . Cytokine . 2007 ; 40 : 216 - 25 .

Ali S , Huber M , Kollewe C , Bischoff SC , Falk W , Martin MU . IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells . Proc Natl Acad Sci U S A . 2007 ; 104 : 18660 - 5 .

Iikura M , Suto H , Kajiwara N , Oboki K , Ohno T , Okayama Y , et al . IL-33 can promote survival adhesion and cytokine production in human mast cells . Lab Invest . 2007 ; 87 : 971 - 8 .

Allakhverdi Z , Smith DE , Comeau MR , Delespesse G . Cutting edge: the ST2 ligand IL-33 potently activates and drives maturation of human mast cells . J Immunol . 2007 ; 179 : 2051 - 4 .

Andrade MV , Iwaki S , Ropert C , Gazzinelli RT , Cunha-Melo JR , Beaven MA . Amplification of cytokine production through synergistic activation of NFAT and AP-1 following stimulation ofmast cells with antigen and IL-33 . Eur J Immunol . 2011 ; 41 : 760 - 72 .

Silver MR , Margulis A , Wood N , Goldman SJ , Kasaian M , Chaudhary D . IL-33 synergizes with IgE-dependent and IgE-independent agents to promote mast cell and basophil activation . Inflamm Res . 2010 ; 59 : 207 - 18 .

Morita H , Arae K , Unno H , Miyauchi K , Toyama S , Nambu A , et al . An interleukin-33-mast cell-interleukin-2 axis suppresses papain-induced allergic inflammation by promoting regulatory T cell numbers . Immunity . 2015 ; 43 : 175 - 86 .

Smithgall MD , Comeau MR , Yoon BR , Kaufman D , Armitage R , Smith DE . IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK cells . Int Immunol . 2008 ; 20 : 1019 - 30 .

Pecaric-Petkovic T , Didichenko SA , Kaempfer S , Spiegl N , Dahinden CA . Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33 . Blood . 2009 ; 113 : 1526 - 34 .

Suzukawa M , Iikura M , Koketsu R , Nagase H , Tamura C , Komiya A , et al . An IL-1 cytokine member, IL-33, induces human basophil activation via its ST2 receptor . J Immunol . 2008 ; 181 : 5981 - 9 .

Suzukawa M , Koketsu R , Iikura M , Nakae S , Matsumoto K , Nagase H . Interleukin-33 enhances adhesion, CD11b expression and survival in human eosinophils . Lab Invest . 2008 ; 88 : 1245 - 53 .

Cherry WB , Yoon J , Bartemes KR , Iijima K , Kita H . A novel IL-1 family cytokine, IL-33, potently activates human eosinophils . J Allergy Clin Immunol . 2008 ; 121 : 1484 - 90 .

Ohno T , Morita H , Arae K , Matsumoto K , Nakae S . Interleukin-33 in allergy . Allergy . 2012 ; 67 : 1203 - 14 .

Kurowska-Stolarska M , Stolarski B , Kewin P , Murphy G , Corrigan CJ , Ying S , et al . IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation . J Immunol . 2009 ; 183 : 6469 - 77 .

Besnard AG , Togbe D , Guillou N , Erard F , Quesniaux V , Ryffel B . IL-33-activated dendritic cells are critical for allergic airway inflammation . Eur J Immunol . 2011 ; 41 : 1675 - 86 .

Rank MA , Kobayashi T , Kozaki H , Bartemes KR , Squillace DL , Kita H . IL-33-activated dendritic cells induce an atypical TH2-type response . J Allergy Clin Immunol . 2009 ; 123 : 1047 - 54 .

Matta BM , Lott JM , Mathews LR , Liu Q , Rosborough BR , Blazar BR , et al . IL-33 is an unconventional alarmin that stimulates IL-2 secretion by dendritic cells to selectively expand IL-33R/ST2+ regulatory T cells . J Immunol . 2014 ; 193 : 4010 - 20 .

Martinez-Gonzalez I , Steer CA , Takei F . Lung ILC2s link innate and adaptive responses in allergic inflammation . Trends Immunol . 2015 ; 36 : 189 - 95 .

Halim TY , Steer CA , Mathä L , Gold MJ , Martinez-Gonzalez I , McNagny KM , et al . Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation . Immunity . 2014 ; 40 : 425 - 35 .

Barlow JL , McKenzie AN . Nuocytes: expanding the innate cell repertoire in type-2 immunity . J Leukoc Biol . 2011 ; 90 : 867 - 74 .

Neill DR , Wong SH , Bellosi A , Flynn RJ , Daly M , Langford TK . Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity . Nature . 2010 ; 464 : 1367 - 70 .

Barlow JL , Bellosi A , Hardman CS , Drynan LF , Wong SH , Cruickshank JP , et al . Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity . J Allergy Clin Immunol . 2012 ; 129 : 191-8-e1-4 .

Chang YJ , Kim HY , Albacker LA , Baumgarth N , McKenzie AN , Smith DE , et al . Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity . Nat Immunol . 2011 ; 12 : 631 - 8 .

Bartemes KR , Iijima K , Kobayashi T , Kephart GM , McKenzie AN , Kita H . IL-33-responsive lineage− CD25+ CD44(hi) lymphoid cells mediate innate type 2 immunity and allergic inflammation in the lungs . J Immunol . 2012 ; 188 : 1503 - 13 .

Rak GD , Osborne LC , Siracusa MC , Kim BS , Wang K , Bayat A , et al . IL-33-dependent group 2 innate lymphoid cells promote cutaneous wound healing . J Invest Dermatol . 2016 ; 136 : 487 - 96 .

Besnard AG , Guabiraba R , Niedbala W , Palomo J , Reverchon F , Shaw TN , et al . IL-33-mediated protection against experimental cerebral malaria is linked to induction of type 2 innate lymphoid cells, M2 macrophages and regulatory T cells . PLoS Pathog . 2015 ; 11 : e1004607 .

Hung LY , Lewkowich IP , Dawson LA , Downey J , Yang Y , Smith DE , et al . IL-33 drives biphasic IL-13 production for noncanonical type 2 immunity against hookworms . Proc Natl Acad Sci U S A . 2013 ; 110 : 282 - 7 .

Yang Q , Li G , Zhu Y , Liu L , Chen E , Turnquist H . IL-33 synergizes with TCR and IL-12 signaling to promote the effector function of CD8+ T cells . Eur J Immunol . 2011 ; 41 : 3351 - 60 .

Bourgeois E , Van LP , Samson M , Diem S , Barra A , Roga S , et al . The pro-Th2 cytokine IL-33 directly interacts with invariant NKT and NK cells to induce IFN-gamma production . Eur J Immunol . 2009 ; 39 : 1046 - 55 .

Çekmez F , Fidanci MK , Ayar G , Saldir M , Karaoglu A , Gündüz RC , et al . Diagnostic value of upar, IL-33, and ST2 levels in childhood sepsis . Clin Lab . 2016 ; 62 : 751 - 5 .

Brunner M , Krenn C , Roth G , Moser B , Dworschak M , Jensen-Jarolim E , et al . Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma . Intensive Care Med . 2004 ; 30 : 1468 - 73 .

Hoogerwerf JJ , Tanck MW , van Zoelen MA , Wittebole X , Laterre PF , van der Poll T . Soluble ST2 plasma concentrations predict mortality in severe sepsis . Intensive Care Med . 2010 ; 36 : 630 - 7 .

Hur M , Kim H , Kim HJ , Yang HS , Magrini L , Marino R , et al . Soluble ST2 has a prognostic role in patients with suspected sepsis . Ann Lab Med . 2015 ; 35 : 570 - 7 .

Parenica J , Malaska J , Jarkovsky J , Lipkova J , Dastych M , Helanova K , et al . Soluble ST2 levels in patients with cardiogenic and septic shock are not predictors of mortality . Exp Clin Cardiol . 2012 ; 17 : 205 - 9 .

Brint EK , Xu D , Liu H , Dunne A , McKenzie AN , O’Neill LA , et al . ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance . Nat Immunol . 2004 ; 5 : 373 - 9 .

Liu J , Buckley JM , Redmond HP , Wang JH . ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein- induced tolerance . J Immunol . 2010 ; 184 : 5802 - 8 .

Espinassous Q , Garcia-de-Paco E , Garcia-Verdugo I , Synguelakis M , von Aulock S , Sallenave JM , et al . IL-33 enhances lipopolysaccharide-induced inflammatory cytokine production from mouse macrophages by regulating lipopolysaccharide receptor complex . J Immunol . 2009 ; 183 : 1446 - 55 .

Oboki K , Ohno T , Kajiwara N , Saito H , Nakae S . IL-33 and IL-33 receptors in host defense and diseases . Allergol Int . 2010 ; 59 : 143 - 60 .

Xiang Y , Eyers F , Herbert C , Tay HL , Foster PS , Yang M . MicroRNA-487b is a negative regulator of macrophage activation by targeting IL-33 production . J Immunol . 2016 ; 196 : 3421 - 8 .

Ohno T , Oboki K , Morita H , Kajiwara N , Arae K , Tanaka S , et al . Paracrine IL-33 stimulation enhances lipopolysaccharide-mediated macrophage activation . PLoS One . 2011 ; 6 : e18404 .

Sweet MJ , Leung BP , Kang D , Sogaard M , Schulz K , Trajkovic V , et al . A novel pathway regulating lipopolysaccharide-induced shock by ST2/T1 via inhibition of Toll-like receptor 4 expression . J Immunol . 2001 ; 166 : 6633 - 9 .

Takezako N , Hayakawa M , Hayakawa H , Aoki S , Yanagisawa K , Endo H , et al . ST2 suppresses IL-6 production via the inhibition of IkappaB degradation induced by the LPS signal in THP-1 cells . Biochem Biophys Res Commun . 2006 ; 341 : 425 - 32 .

Nagata A , Takezako N , Tamemoto H , Ohto-Ozaki H , Ohta S , Tominaga S , et al . Soluble ST2 protein inhibits LPS stimulation on monocyte-derived dendritic cells . Cell Mol Immunol . 2012 ; 9 : 399 - 409 .

Nabe T , Wakamori H , Yano C , Nishiguchi A , Yuasa R , Kido H , et al . Production of interleukin (IL)-33 in the lungs during multiple antigen challenge-induced airway inflammation in mice, and its modulation by a glucocorticoid . Eur J Pharmacol . 2015 ; 757 : 34 - 41 .

Stier MT , Goleniewska K , Peebles RS . Respiratory syncytial virus induces IL-25 and IL-33 production in the lungs . J Allergy Clin Immun . 2014 ; 133 : AB53 .

Martínez-González I , Roca O , Masclans JR , Moreno R , Salcedo MT , Baekelandt V , et al . Human mesenchymal stem cells overexpressing the IL-33 antagonist soluble IL-1 receptor-like-1 attenuate endotoxin-induced acute lung injury . Am J Respir Cell Mol Biol . 2013 ; 49 : 552 - 62 .

Yin H , Li XY , Yuan BH , Zhang BB , Hu SL , Gu HB , et al . Adenovirus-mediated overexpression of soluble ST2 provides a protective effect on lipopolysaccharideinduced acute lung injury in mice . Clin Exp Immunol . 2011 ; 164 : 248 - 55 .

Hoogerwerf JJ , Leendertse M , Wieland CW , de Vos AF , de Boer JD , Florquin S , et al . Loss of suppression of tumorigenicity 2 (ST2) gene reverses sepsisinduced inhibition of lung host defense in mice . Am J Respir Crit Care Med . 2011 ; 183 : 932 - 40 .

Buckley JM , Liu JH , Li CH , Blankson S , Wu QD , Jiang Y , et al . Increased susceptibility of ST2-deficient mice to polymicrobial sepsis is associated with an impaired bactericidal function . J Immunol . 2011 ; 187 : 4293 - 9 .

Blok DC , de Vos AF , Florquin S , van der Poll T . Role of interleukin 1 receptor like 1 (ST2) in gram-negative and gram-positive sepsis in mice . Shock . 2013 ; 40 : 290 - 6 .

Alves-Filho JC , Sonego F , Souto FO , Freitas A , Verri Jr WA , Auxili-Adora-Martins M , et al . Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection . Nat Med . 2010 ; 16 : 708 - 12 .

Li S , Zhu FX , Zhao XJ , An YZ . The immunoprotective activity of interleukin-33 in mouse model of cecal ligation and puncture-induced sepsis . Immunol Lett . 2016 ; 169 : 1 - 7 .

Lan F , Yuan B , Liu T , Luo X , Huang P , Liu Y , et al . Interleukin-33 facilitates neutrophil recruitment and bacterial clearance in S. aureus-caused peritonitis . Mol Immunol . 2016 ; 72 : 74 - 80 .

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