Systemic administration of IL-33 induces a population of circulating KLRG1hi type 2 innate lymphoid cells and inhibits type 1 innate immunity against multiple myeloma
Corresponding Author
Camille Guillerey
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
School of Medicine, The University of Queensland, Herston, QLD, Australia
Correspondence
Camille Guillerey, Cancer Immunotherapies Laboratory, Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, QLD 4101, Australia.
E-mail: [email protected]
Search for more papers by this authorKimberley Stannard
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorJason Chen
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
School of Medicine, The University of Queensland, Herston, QLD, Australia
Search for more papers by this authorSophie Krumeich
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorKim Miles
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorKyohei Nakamura
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorJessica Smith
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
School of Environment and Sciences, Griffith University, Brisbane, QLD, Australia
Search for more papers by this authorYuan Yu
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorSusanna Ng
Immunology and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorHeidi Harjunpää
School of Medicine, The University of Queensland, Herston, QLD, Australia
Cancer Immunoregulation and Immunotherapy Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorMichele WL Teng
Cancer Immunoregulation and Immunotherapy Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorChristian Engwerda
Immunology and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorGabrielle T Belz
Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC, Australia
Search for more papers by this authorMark J Smyth
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
School of Medicine, The University of Queensland, Herston, QLD, Australia
Search for more papers by this authorCorresponding Author
Camille Guillerey
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
School of Medicine, The University of Queensland, Herston, QLD, Australia
Correspondence
Camille Guillerey, Cancer Immunotherapies Laboratory, Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, QLD 4101, Australia.
E-mail: [email protected]
Search for more papers by this authorKimberley Stannard
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorJason Chen
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
School of Medicine, The University of Queensland, Herston, QLD, Australia
Search for more papers by this authorSophie Krumeich
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorKim Miles
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorKyohei Nakamura
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorJessica Smith
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
School of Environment and Sciences, Griffith University, Brisbane, QLD, Australia
Search for more papers by this authorYuan Yu
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorSusanna Ng
Immunology and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorHeidi Harjunpää
School of Medicine, The University of Queensland, Herston, QLD, Australia
Cancer Immunoregulation and Immunotherapy Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorMichele WL Teng
Cancer Immunoregulation and Immunotherapy Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorChristian Engwerda
Immunology and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Search for more papers by this authorGabrielle T Belz
Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC, Australia
Search for more papers by this authorMark J Smyth
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
School of Medicine, The University of Queensland, Herston, QLD, Australia
Search for more papers by this authorAbstract
Type 2 innate lymphoid cells (ILC2s) are important producers of type 2 cytokines whose role in hematological cancers remains unclear. ILC2s are a heterogeneous population encompassing distinct subsets with different tissue localization and cytokine responsiveness. In this study, we investigated the role of bone marrow (BM) ILC2s and interleukin (IL)-33-stimulated ILC2s in multiple myeloma, a plasma cell malignancy that develops in the BM. We found that myeloma growth was associated with phenotypic and functional alterations of BM ILC2s, characterized by an increased expression of maturation markers and reduced cytokine response to IL-2/IL-33. We identified a population of KLRG1hi ILC2s that preferentially accumulated in the liver and spleen of Il2rg−/− Rag2−/− mice reconstituted with BM ILC2s. A similar population of KLRG1hi ILC2s was observed in the blood, liver and spleen of IL-33-treated wild-type mice. The presence of KLRG1hi ILC2s in ILC2-reconstituted Il2rg−/− Rag2−/− mice or in IL-33-treated wild-type mice was associated with increased eosinophil numbers but had no effect on myeloma progression. Interestingly, while decreased myeloma growth was observed following treatment of Rag-deficient mice with the type 1 cytokines IL-12 and IL-18, this protection was reversed when mice received a combined treatment of IL-33 together with IL-12 and IL-18. In summary, our data indicate that IL-33 treatment induces a population of circulating inflammatory KLRG1hi ILC2s and inhibits type 1 immunity against multiple myeloma. These results argue against therapeutic administration of IL-33 to myeloma patients.
CONFLICT OF INTEREST
MJS has research agreements with Bristol Myers Squibb and Tizona Therapeutics. All other authors declare that they have no conflict of interest.
Supporting Information
| Filename | Description |
|---|---|
| imcb12390-sup-0001-FigS1-10.pdfPDF document, 1.2 MB | Supplementary figures 1-10 |
| imcb12390-sup-0002-TableS1.docxWord document, 19 KB | Supplementary table 1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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