Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity

Nature Immunology volume 17, pages 646–655 (2016)Cite this article

Subjects

An Erratum to this article was published on 19 July 2016

This article has been updated

Abstract

Group 2 innate lymphoid cells (ILC2 cells) are important for type 2 immune responses and are activated by the epithelial cytokines interleukin 33 (IL-33), IL-25 and thymic stromal lymphopoietin (TSLP). Here we demonstrated that IL-1β was a critical activator of ILC2 cells, inducing proliferation and cytokine production and regulating the expression of epithelial cytokine receptors. IL-1β also governed ILC2 plasticity by inducing low expression of the transcription factor T-bet and the cytokine receptor chain IL-12Rβ2, which enabled the conversion of these cells into an ILC1 phenotype in response to IL-12. This transition was marked by an atypical chromatin landscape characterized by the simultaneous transcriptional accessibility of the locus encoding interferon-γ (IFN-γ) and the loci encoding IL-5 and IL-13. Finally, IL-1β potentiated ILC2 activation and plasticity in vivo, and IL-12 acted as the switch that determined an ILC2-versus-ILC1 response. Thus, we have identified a previously unknown role for IL-1β in facilitating ILC2 maturation and plasticity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: IL-1 is a potent activator of human ILC2 cells.
Figure 2: IL-1β enhances ILC2 responsiveness to IL-33, IL-25 and TSLP.
Figure 3: IL-1β activates ILC2s via IL-1R1 and NF-κB.
Figure 4: Dynamic transcriptome changes in ILC2 cells are induced by IL-1β.
Figure 5: Differentiation of ILC2 cells into ILC1-like cell occurs following priming with IL-1β.
Figure 6: IL-1β imparts a hybrid epigenetic landscape in ILC2s.
Figure 7: In vivo regulation of ILC2 plasticity by IL-1.

Similar content being viewed by others

Accession codes

Primary accessions

Gene Expression Omnibus

Change history

  • 29 April 2016

    In the version of this article initially published online, the interferon (IFN-α) in the fourth sentence of the abstract is incorrect. That section should read "the locus encoding interferon-γ (IFN-γ)...." Also, sentence two in paragraph three of the introduction includes a typographical error ("zand"); that should read "IL-18 and IL-1...." The errors have been corrected for the print, PDF and HTML versions of this article.

References

  1. Sonnenberg, G.F. & Artis, D. Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat. Med. 21, 698–708 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Neill, D.R. et al. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464, 1367–1370 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Moro, K. et al. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells. Nature 463, 540–544 (2010).

    CAS  PubMed  Google Scholar 

  4. Price, A.E. et al. Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proc. Natl. Acad. Sci. USA 107, 11489–11494 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Tait Wojno, E.D. & Artis, D. Innate lymphoid cells: balancing immunity, inflammation, and tissue repair in the intestine. Cell Host Microbe 12, 445–457 (2012).

    CAS  PubMed  Google Scholar 

  6. Lee, M.W. et al. Activated type 2 innate lymphoid cells regulate beige fat biogenesis. Cell 160, 74–87 (2015).

    CAS  PubMed  Google Scholar 

  7. Brestoff, J.R. et al. Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature 519, 242–246 (2015).

    CAS  PubMed  Google Scholar 

  8. Oliphant, C.J. et al. 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 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Halim, T.Y. et al. Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. Immunity 40, 425–435 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Salimi, M. et al. A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. J. Exp. Med. 210, 2939–2950 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Kim, B.S. et al. TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation. Sci. Transl. Med. 5, 170ra16 (2013).

    PubMed  PubMed Central  Google Scholar 

  12. Hams, E. et al. IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis. Proc. Natl. Acad. Sci. USA 111, 367–372 (2014).

    CAS  PubMed  Google Scholar 

  13. McHedlidze, T. et al. Interleukin-33-dependent innate lymphoid cells mediate hepatic fibrosis. Immunity 39, 357–371 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Spits, H. et al. Innate lymphoid cells–a proposal for uniform nomenclature. Nat. Rev. Immunol. 13, 145–149 (2013).

    CAS  PubMed  Google Scholar 

  15. Walker, J.A., Barlow, J.L. & McKenzie, A.N.J. Innate lymphoid cells–how did we miss them? Nat. Rev. Immunol. 13, 75–87 (2013).

    CAS  PubMed  Google Scholar 

  16. Klose, C.S.N. et al. A T-bet gradient controls the fate and function of CCR6−RORγt+ innate lymphoid cells. Nature 494, 261–265 (2013).

    CAS  PubMed  Google Scholar 

  17. Bernink, J.H. et al. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat. Immunol. 14, 221–229 (2013).

    CAS  PubMed  Google Scholar 

  18. Bernink, J.H. et al. Interleukin-12 and -23 control plasticity of CD127+ group 1 and group 3 innate lymphoid cells in the intestinal lamina propria. Immunity 43, 146–160 (2015).

    CAS  PubMed  Google Scholar 

  19. Mjösberg, J.M. et al. Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat. Immunol. 12, 1055–1062 (2011).

    Article  CAS  PubMed  Google Scholar 

  20. Garlanda, C., Dinarello, C.A. & Mantovani, A. The interleukin-1 family: back to the future. Immunity 39, 1003–1018 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Mortha, A. et al. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343, 1249288 (2014).

    PubMed  PubMed Central  Google Scholar 

  22. Monticelli, L.A. et al. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat. Immunol. 12, 1045–1054 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Barlow, J.L. et al. IL-33 is more potent than IL-25 in provoking IL-13-producing nuocytes (type 2 innate lymphoid cells) and airway contraction. J. Allergy Clin. Immunol. 132, 933–941 (2013).

    CAS  PubMed  Google Scholar 

  24. Hazenberg, M.D. & Spits, H. Human innate lymphoid cells. Blood 124, 700–709 (2014).

    CAS  PubMed  Google Scholar 

  25. Munneke, J.M. et al. Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease. Blood 124, 812–821 (2014).

    CAS  PubMed  Google Scholar 

  26. Suzukawa, M. et al. An IL-1 cytokine member, IL-33, induces human basophil activation via its ST2 receptor. J. Immunol. 181, 5981–5989 (2008).

    CAS  PubMed  Google Scholar 

  27. Pecaric-Petkovic, T., Didichenko, S.A., Kaempfer, S., Spiegl, N. & Dahinden, C.A. Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33. Blood 113, 1526–1534 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Halim, T.Y. et al. Retinoic-acid-receptor-related orphan nuclear receptor α is required for natural helper cell development and allergic inflammation. Immunity 37, 463–474 (2012).

    CAS  PubMed  Google Scholar 

  29. Walker, J.A. et al. Bcl11b is essential for group 2 innate lymphoid cell development. J. Exp. Med. 212, 875–882 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Yu, Y. et al. The transcription factor Bcl11b is specifically expressed in group 2 innate lymphoid cells and is essential for their development. J. Exp. Med. 212, 865–874 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Califano, D. et al. Transcription factor Bcl11b controls identity and function of mature type 2 innate lymphoid cells. Immunity 43, 354–368 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Fuchs, A. et al. Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-γ-producing cells. Immunity 38, 769–781 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Wilson, C.B., Rowell, E. & Sekimata, M. Epigenetic control of T-helper-cell differentiation. Nat. Rev. Immunol. 9, 91–105 (2009).

    CAS  PubMed  Google Scholar 

  34. Hoyler, T. et al. The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity 37, 634–648 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Björklund, A.K. et al. The heterogeneity of human CD127+ innate lymphoid cells revealed by single-cell RNA sequencing. Nat. Immunol. 17, 451–460 (2016).

    PubMed  Google Scholar 

  36. Yagi, R. et al. The transcription factor GATA3 is critical for the development of all IL-7Rα-expressing innate lymphoid cells. Immunity 40, 378–388 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Nussbaum, J.C. et al. Type 2 innate lymphoid cells control eosinophil homeostasis. Nature 502, 245–248 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Silver, J.S. et al. Inflammatory triggers associated with exacerbations of chronic obstructive pulmonary disease orchestrate plasticity of group 2 innate lymphoid cells in the lungs. Nat. Immunol. 10.1038/ni.3443 (2016).

  39. Bal, S.M. et al. IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation. Nat. Immunol. 10.1038/ni.3444 (2016).

  40. Sims, J.E. & Smith, D.E. The IL-1 family: regulators of immunity. Nat. Rev. Immunol. 10, 89–102 (2010).

    CAS  PubMed  Google Scholar 

  41. Kearley, J. et al. Cigarette smoke silences innate lymphoid cell function and facilitates an exacerbated type I interleukin-33-dependent response to infection. Immunity 42, 566–579 (2015).

    CAS  PubMed  Google Scholar 

  42. Turner, J.E. et al. IL-9-mediated survival of type 2 innate lymphoid cells promotes damage control in helminth-induced lung inflammation. J. Exp. Med. 210, 2951–2965 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Hepworth, M.R. et al. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature 498, 113–117 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Wenzel, S.E. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat. Med. 18, 716–725 (2012).

    CAS  PubMed  Google Scholar 

  45. Lambrecht, B.N. & Hammad, H. The immunology of asthma. Nat. Immunol. 16, 45–56 (2015).

    CAS  PubMed  Google Scholar 

  46. Randolph, D.A., Stephens, R., Carruthers, C.J. & Chaplin, D.D. Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation. J. Clin. Invest. 104, 1021–1029 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Hansen, G., Berry, G., DeKruyff, R.H. & Umetsu, D.T. Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation. J. Clin. Invest. 103, 175–183 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Nakao, F. et al. Association of IFN-gamma and IFN regulatory factor 1 polymorphisms with childhood atopic asthma. J. Allergy Clin. Immunol. 107, 499–504 (2001).

    CAS  PubMed  Google Scholar 

  49. Yu, M. et al. Identification of an IFN-γ/mast cell axis in a mouse model of chronic asthma. J. Clin. Invest. 121, 3133–3143 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Sugimoto, T. et al. Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse. J. Exp. Med. 199, 535–545 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Soumelis, V. et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat. Immunol. 3, 673–680 (2002).

    CAS  PubMed  Google Scholar 

  52. Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36 (2013).

    PubMed  PubMed Central  Google Scholar 

  53. Anders, S., Pyl, P.T. & Huber, W. HTSeq–a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015).

    CAS  PubMed  Google Scholar 

  54. Harrow, J. et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 22, 1760–1774 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Robinson, M.D., McCarthy, D.J. & Smyth, G.K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010).

    CAS  PubMed  Google Scholar 

  56. Roederer, M., Nozzi, J.L. & Nason, M.C. SPICE: exploration and analysis of post-cytometric complex multivariate datasets. Cytometry A 79, 167–174 (2011).

    PubMed  PubMed Central  Google Scholar 

  57. Kozuka, T., Sugita, M., Shetzline, S., Gewirtz, A.M. & Nakata, Y. c-Myb and GATA-3 cooperatively regulate IL-13 expression via conserved GATA-3 response element and recruit mixed lineage leukemia (MLL) for histone modification of the IL-13 locus. J. Immunol. 187, 5974–5982 (2011).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank H. Ueno, S. Hanabuchi, T. Kim and M. Ramaswamy for discussions; C. Harrod and C. Kiefer for critical reading of the manuscript; N. Loof, C. Boudreaux, K. Kayembe, C. Groves and R. Rayanki for support with cell sorting; H. Lu and A. Berlin for laboratory support; the LAR staff for maintaining the experimental animals; N. Baldwin for help in depositing RNA-sequencing data; and A. O'Bar and S. Zurawski for performing Luminex experiment. Supported by the Cancer Prevention and Research Institute of Texas (RP110319 (“Targeting Dendritic Cells to Block Immunosuppression in Breast Cancer”) to Y.-J.L.) and by the Japan Society for the Promotion of Science (KAKENHI Grant-in-Aid 23-10890 to Y.O.)

Author information

Authors and Affiliations

  1. Baylor Research Institute, Baylor Scott and White Health, Dallas, Texas, USA

    Yoichiro Ohne, LuAnn Thompson-Snipes, Magalie A Collet, Jean Philippe Blanck, Brandi L Cantarel & Yong-Jun Liu

  2. R&D Research, MedImmune, Gaithersburg, Maryland, USA

    Yoichiro Ohne & Yong-Jun Liu

  3. Department of Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, Maryland, USA

    Jonathan S Silver, Alan M Copenhaver & Alison A Humbles

Authors
  1. Yoichiro Ohne
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan S Silver
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. LuAnn Thompson-Snipes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Magalie A Collet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean Philippe Blanck
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Brandi L Cantarel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alan M Copenhaver
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alison A Humbles
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yong-Jun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.O. and Y.-J.L. conceived of the idea for this project; Y.O., J.S.S., L.T.-S., A.A.H. and Y.-J.L. designed experiments; Y.O., J.S.S., L.T.-S., M.A.C., J.P.B. and A.M.C. performed experiments and analyzed data; Y.O. and B.L.C. performed analysis of RNA sequencing data; and Y.O., J.S.S., L.T.-S., A.H.H. and Y.-J.L. wrote the manuscript.

Corresponding authors

Correspondence to Alison A Humbles or Yong-Jun Liu.

Ethics declarations

Competing interests

Y.O., J.S.S., A.M.C., A.A.H. and Y.-J.L. are employed by and shareholders of Medimmune.

Integrated supplementary information

Supplementary Figure 1 Identification of human ILC2s in peripheral blood and tonsils.

(a) List of cytokines tested for the ability to promote proliferation of ILC2s. (b) Expression of T-bet and GATA-3 in ILCs in PBMC examined by intra-nuclear transcription staining followed by flow cytometry. Subsets of ILCs were defined as in Fig. 1a. (c) Purity and yield of ILC2s from blood after cell sorting. (d) Purity and yield ILC2s after FACS sorting. (e) Schematic of identification of ILCs in human tonsils by flow cytometry. Antibodies against the following lineage makers (Lin) are used: CD3, CD4, CD14, CD16, CD19, CD20, CD34, CD123, TCRαβ, HLA-DR. ILC2s were identified as Lin- CD127+ CD56- CRTH2+. CD56brigtht NK cells were identified as Lin-CD127int c-Kit- CD56hi.

Supplementary Figure 2 IL-1β enhances the response of ILC2s to epithelial cytokines.

(a) Expression of CRLF2 in CD56brigtht NK cells, ILC2s and c-Kit+ CD127+ cells freshly isolated from peripheral blood or stimulated with IL-2 and IL-1β for 7 days. Expression of CRLF2 was normalized to GUSB and shown as arbitrary unit. (b) Cell numbers of ILC2s recovered after culturing with IL-2, IL-25 and IL-1β for 7 days (300 cells plated per well at day 0). (c) Scheme of the experiments comparing freshly isolated ILC2s and IL-1β-primed ILC2s. (d) Frequencies of phospho-NF-κB positive cells in Fig. 3f. (e) NF-κB phosphorylation in CD56brigtht NK cells, ILC2s and c-Kit+ CD127+ cells in freshly isolated from peripheral blood stimulated with IL-1β, IL-18 and IL-33 for 5 min. *P < 0.05, **P < 0.01 and *** P < 0.001 using one-way ANOVA followed by two-tailed t-test (a), one-way ANOVA followed by Dunnet’s test (b), or followed by Turkey’s test (d). Data are from 6 (a) and 5 (b) and 4 (d) independent experiments with independent donors or from one experiment representative of four (e) experiments with similar results. Data are represented as mean (± s.e.m.) (a,b).

Supplementary Figure 3 Validation of the expression changes in ILC2s stimulated with IL-1β.

(a) The surface expression of HLA-DR/DP/DQ, CD80 and CD40L measured by flow cytometry in ILC2s freshly isolated from peripheral blood or cultured with IL-2 and IL-1β for 7 days. (b) mRNA levels of GATA3, RORC and RORA in freshly isolated ILC2s, CD56bright NK cells and ILC2s stimulated with IL-2 and IL-1β for 5 days. Data are normalized to GUSB and shown as relative values and represented as mean (± s.e.m.). *P<0.05, ** P < 0.01, *** P < 0.001 analyzed using one-way ANOVA followed by Turkey’s test (b). Data are representative of 6 experiments with similar results (a), or 6 (b) experiments with independent donors.

Supplementary Figure 4 IL-12 affects ILC2 functional gene expression and phenotype plasticity.

(a) Viabilities of ILC2s cultured with IL-2 and IL-1β with or without IL-12 for 7 days. (b) Schematic of identification of human c-Kit+ and c-Kit- subpopulations of ILC2s in human PBMC by flow cytometry. CD56brigtht NK cells and ILC2s were defined as in Fig. 1a and ILC2s were further divided by expression of c-Kit. Numbers adjacent to outlined areas indicate percent of parent population. (c) Recovery of c-Kit+ and c-Kit- ILC2s subpopulations from 150 ml whole blood. (d) Intracellular staining of IL-13, IL-5 and IFN-γ in c-Kit+ and c-Kit- ILC2s, and CD56brigtht NK cells cultured with or without IL-12 in the presence of IL-2 and IL-1β for 7 days followed by re-stimulation with PMA and ionomycin for 6 h in the presence of protein secretion inhibitors. (e) Frequencies of IL-5 and IL-13 double positive cells (left) and IFN-γ and IL-13 double positive cells (right) measured in d. (f) Expression of IL1RL1, IL17RB, CRLF2 and GATA3 in ILC2s freshly isolated from peripheral blood or cultured with IL-2 and IL-1β with or without IL-12 for 7 days. Data are normalized to GUSB and shown as relative values. * P < 0.05, **P < 0.01 and ***P < 0.001 as analyzed by two-tailed t-test (a), one-way ANOVA followed by Turkey’s test (e,f). Data are from 9 (a) or 6 (c,e,f) experiments with independent donors or from one experiment representative of 6 experiments (d) with similar results. Data are represented as mean (± s.e.m.) (f).

Supplementary Figure 5 IFNG and type-2-cytokine-encoding loci.

(a) IFNG locus and (b) Type 2 cytokine loci are shown with gray boxes depicting the distal regulatory regions for each locus. The red boxes approximately refer to the regions amplified by qPCR using specific primers as shown in Fig. 6. CNS, conserved non-coding sequences. CGRE, conserved GATA-3 response element. IE, IL4 intronic enhancer. HS, hyper sensitive site.

Supplementary Figure 6 Identification of ILC2 cells and NK cells in vivo and the effect of anti-IL-12 on IL-1-mediated ILC2 activation.

(a) The expression of lineage markers CD3, CD19, B220, CD5, TCRβ, TCRγδ, CD11c, F4/80, Gr1, Ter119, and CD27 on CD45+ cells, ILC2s and CD49b+ NKs measured by flow cytometry. (b) The concentration of IL-13 in the culture supernatant of ILC2 isolated from the lungs of the mice administered and stimulated as in Fig. 7g. Data are representative of 7 independent experiments (a). Data are represented as mean (b).

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6 and Supplementary Tables 1–4 (PDF 1150 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ohne, Y., Silver, J., Thompson-Snipes, L. et al. IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity. Nat Immunol 17, 646–655 (2016). https://doi.org/10.1038/ni.3447

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni.3447

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing