BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Interleukin-2/antibody complex expanding Foxp3+ regulatory T cells exacerbates Th2-mediated allergic airway inflammation

  • Hong, Sung-Wook (Academy of Immunology and Microbiology, Institute for Basic Science (IBS)) ;
  • O, Eunju (Academy of Immunology and Microbiology, Institute for Basic Science (IBS)) ;
  • Lee, Jun Young (Academy of Immunology and Microbiology, Institute for Basic Science (IBS)) ;
  • Yi, Jaeu (Academy of Immunology and Microbiology, Institute for Basic Science (IBS)) ;
  • Cho, Kyungjin (Academy of Immunology and Microbiology, Institute for Basic Science (IBS)) ;
  • Kim, Juhee (Academy of Immunology and Microbiology, Institute for Basic Science (IBS)) ;
  • Kim, Daeun (Academy of Immunology and Microbiology, Institute for Basic Science (IBS)) ;
  • Surh, Charles D. (Academy of Immunology and Microbiology, Institute for Basic Science (IBS)) ;
  • Kim, Kwang Soon (Academy of Immunology and Microbiology, Institute for Basic Science (IBS))
  • Received : 2018.11.26
  • Accepted : 2019.03.12
  • Published : 2019.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

$Foxp3^+$ regulatory $CD4^+$ T (Treg) cells play an essential role in preventing overt immune responses against self and innocuous foreign antigens. Selective expansion of endogenous Treg cells in response to the administration of interleukin (IL)-2/antibody complex, such as the IL-2/JES6-1 complex (IL-2C) in mice, is considered an attractive therapeutic approach to various immune disorders. Here, we investigated the therapeutic potential of IL-2C in allergic airway inflammation models. IL-2C treatment ameliorated Th17-mediated airway inflammation; however, unexpectedly, IL-2C treatment exacerbated Th2-mediated allergic airway inflammation by inducing the selective expansion of Th2 cells and type-2 innate lymphoid cells. We also found that IL-2 signaling is required for the expansion of Th2 cells in lymphoproliferative disease caused by Treg cell depletion. Our data suggest that IL-2C is selectively applicable to the treatment of allergic airway diseases depending on the characteristics of airway inflammation.

Keywords

References

  1. Josefowicz SZ, Lu LF and Rudensky AY (2012) Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 30, 531-564 https://doi.org/10.1146/annurev.immunol.25.022106.141623
  2. Noval Rivas M and Chatila TA (2016) Regulatory T cells in allergic diseases. J Allergy Clin Immunol 138, 639-652 https://doi.org/10.1016/j.jaci.2016.06.003
  3. Thorburn AN and Hansbro PM (2010) Harnessing regulatory T cells to suppress asthma: from potential to therapy. Am J Respir Cell Mol Biol 43, 511-519 https://doi.org/10.1165/rcmb.2009-0342TR
  4. Mamessier E, Nieves A, Lorec AM et al (2008) T-cell activation during exacerbations: a longitudinal study in refractory asthma. Allergy 63, 1202-1210 https://doi.org/10.1111/j.1398-9995.2008.01687.x
  5. Kearley J, Barker JE, Robinson DS and Lloyd CM (2005) Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4＋CD25＋ regulatory T cells is interleukin 10 dependent. J Exp Med 202, 1539-1547 https://doi.org/10.1084/jem.20051166
  6. Liao W, Lin JX and Leonard WJ (2011) IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr Opin Immunol 23, 598-604 https://doi.org/10.1016/j.coi.2011.08.003
  7. Boyman O, Kovar M, Rubinstein MP, Surh CD and Sprent J (2006) Selective stimulation of T cell subsets with antibody-cytokine immune complexes. Science 311, 1924-1927 https://doi.org/10.1126/science.1122927
  8. Spangler JB, Tomala J, Luca VC et al (2015) Antibodies to Interleukin-2 Elicit Selective T Cell Subset Potentiation through Distinct Conformational Mechanisms. Immunity 42, 815-825 https://doi.org/10.1016/j.immuni.2015.04.015
  9. Webster KE, Walters S, Kohler RE et al (2009) In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression. J Exp Med 206, 751-760 https://doi.org/10.1084/jem.20082824
  10. Smaldini PL, Trejo F, Cohen JL, Piaggio E and Docena GH (2018) Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells. Allergy 73, 885-895 https://doi.org/10.1111/all.13402
  11. Wilson MS, Pesce JT, Ramalingam TR, Thompson RW, Cheever A and Wynn TA (2008) Suppression of murine allergic airway disease by IL-2:anti-IL-2 monoclonal antibody-induced regulatory T cells. J Immunol 181, 6942-6954 https://doi.org/10.4049/jimmunol.181.10.6942
  12. Roediger B, Kyle R, Yip KH et al (2013) Cutaneous immunosurveillance and regulation of inflammation by group 2 innate lymphoid cells. Nat Immunol 14, 564-573 https://doi.org/10.1038/ni.2584
  13. Roediger B, Kyle R, Tay SS et al (2015) IL-2 is a critical regulator of group 2 innate lymphoid cell function during pulmonary inflammation. J Allergy Clin Immunol 136, 1653-1663 e1657 https://doi.org/10.1016/j.jaci.2015.03.043
  14. Wesolowska-Andersen A and Seibold MA (2015) Airway molecular endotypes of asthma: dissecting the heterogeneity. Curr Opin Allergy Clin Immunol 15, 163-168 https://doi.org/10.1097/ACI.0000000000000148
  15. Kim YS, Hong SW, Choi JP et al (2009) Vascular endothelial growth factor is a key mediator in the development of T cell priming and its polarization to type 1 and type 17 T helper cells in the airways. J Immunol 183, 5113-5120 https://doi.org/10.4049/jimmunol.0901566
  16. Whitehouse G, Gray E, Mastoridis S et al (2017) IL-2 therapy restores regulatory T-cell dysfunction induced by calcineurin inhibitors. Proc Natl Acad Sci U S A 114, 7083-7088 https://doi.org/10.1073/pnas.1620835114
  17. Kim JM, Rasmussen JP and Rudensky AY (2007) Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol 8, 191-197 https://doi.org/10.1038/ni1428
  18. Laurence A, Tato CM, Davidson TS et al (2007) Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26, 371-381 https://doi.org/10.1016/j.immuni.2007.02.009
  19. Yang XP, Ghoreschi K, Steward-Tharp SM et al (2011) Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol 12, 247-254 https://doi.org/10.1038/ni.1995
  20. Olson MR, Ulrich BJ, Hummel SA et al (2017) Paracrine IL-2 Is Required for Optimal Type 2 Effector Cytokine Production. J Immunol 198, 4352-4359 https://doi.org/10.4049/jimmunol.1601792
  21. Kagami S, Nakajima H, Suto A et al (2001) Stat5a regulates T helper cell differentiation by several distinct mechanisms. Blood 97, 2358-2365 https://doi.org/10.1182/blood.V97.8.2358
  22. Das J, Chen CH, Yang L, Cohn L, Ray P and Ray A (2001) A critical role for NF-kappa B in GATA3 expression and TH2 differentiation in allergic airway inflammation. Nat Immunol 2, 45-50 https://doi.org/10.1038/83158
  23. Garcia S, DiSanto J and Stockinger B (1999) Following the development of a CD4 T cell response in vivo: from activation to memory formation. Immunity 11, 163-171 https://doi.org/10.1016/S1074-7613(00)80091-6
  24. Fallon PG, Ballantyne SJ, Mangan NE et al (2006) Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J Exp Med 203, 1105-1116 https://doi.org/10.1084/jem.20051615
  25. Oliphant CJ, Hwang YY, Walker JA et al (2014) MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion. Immunity 41, 283-295 https://doi.org/10.1016/j.immuni.2014.06.016
  26. Hong SW, Kim KS and Surh CD (2017) Beyond Hygiene: Commensal Microbiota and Allergic Diseases. Immune Netw 17, 48-59 https://doi.org/10.4110/in.2017.17.1.48
  27. Trompette A, Gollwitzer ES, Yadava K et al (2014) Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med 20, 159-166 https://doi.org/10.1038/nm.3444
  28. Lloyd CM, Gonzalo JA, Nguyen T et al (2001) Resolution of bronchial hyperresponsiveness and pulmonary inflammation is associated with IL-3 and tissue leukocyte apoptosis. J Immunol 166, 2033-2040 https://doi.org/10.4049/jimmunol.166.3.2033