Journal article

Systemic administration of IL-33 induces a population of circulating KLRG1(hi)type 2 innate lymphoid cells and inhibits type 1 innate immunity against multiple myeloma

Camille Guillerey, Kimberley Stannard, Jason Chen, Sophie Krumeich, Kim Miles, Kyohei Nakamura, Jessica Smith, Yuan Yu, Susanna Ng, Heidi Harjunpaa, Michele WL Teng, Christian Engwerda, Gabrielle T Belz, Mark J Smyth

Immunology & Cell Biology | WILEY | Published : 2020

Abstract

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 ..

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University of Melbourne Researchers

Grants

Awarded by Priority-driven Collaborative Cancer Research Scheme


Awarded by National Health and Medical Research Council (NHMRC)


Awarded by NHMRC of Australia Early Career Fellowship


Awarded by NHMRC Project Grant


Awarded by Senior Principal Research Fellowship


Awarded by NHMRC


Funding Acknowledgements

The authors thank Liam Town and Kate Elder for breeding, genotyping, maintenance and care of the mice used in this study. We thank the animal house and flow cytometry facilities at QIMR Berghofer Medical Research Institute. We thank Dr Cyril Seillet for helpful suggestions and discussion. This work was funded by a grant (No. 1122183) awarded to CG through the Priority-driven Collaborative Cancer Research Scheme and cofunded by Cancer Australia, Cure Cancer Australia and Can Too Foundation and by a National Health and Medical Research Council (NHMRC) Program Grant (No. 1132519) and Project Grant (No. 1098960) to MJS and MWLT. CG was supported by an NHMRC of Australia Early Career Fellowship (No. 1107417). KN was supported by the Naito Foundation and NHMRC Project Grant (No. 1159593). MJS and GTB were supported by a Senior Principal Research Fellowship (Nos 1078671 and 1135898, respectively). CE was supported by an NHMRC Program Grant (No. 1132975) and Fellowship (No. 1154265).