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Group 2 innate lymphoid cells (ILC2) are regulated by stem cell factor during chronic asthmatic disease

Mucosal Immunologyvolume 12pages445456 (2019) | Download Citation

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Abstract

Stem cell factor (SCF) binds to the receptor c-Kit that is expressed on a number of myeloid and lymphoid cell populations, including Type 2 innate lymphoid cells (ILC2). However the importance of the SCF/c-Kit interaction in ILC2 has not been studied. Here we investigate the role of a specific SCF isoform, SCF248, in the allergic asthmatic response and SCF/c-Kit in ILC2 activation during chronic allergy. We observed that mice treated with a monoclonal antibody specific for SCF248 attenuated the development of chronic asthmatic disease by decreasing the number of mast cells, ILC2 and eosinophils, as well as reducing the accompanying pathogenic cytokine responses. These data were supported using SCFfl/fl-Col1-Cre-ERT mice and W/Wv mice that demonstrated the importance of the stem cell factor/c-Kit activation during chronic allergy and the accumulation of c-kit+ cells. Finally, these data demonstrate for the first time that SCF could activate ILC2 cells in vitro for the production of key allergic cytokines. Together these findings indicate that SCF is a critical cytokine involved in the activation of ILC2 that lead to more severe outcomes during chronic allergy and that the SCF248 isoform could be an important therapeutic target to control the disease progression.

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Acknowledgements

This work was funded in part by NIH grants AI036302 and HL138013. We thank Judith Connett, PhD for editorial review and Gabriela Monzon for artwork.

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Affiliations

  1. Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA

    • Wendy Fonseca
    • , Andrew J Rasky
    • , Catherine Ptaschinski
    • , Susan H. Morris
    • , Shannon K. K. Best
    • , Carrie-Anne Malinczak
    •  & Nicholas W. Lukacs
  2. Opsidio, LLC, Bryn Mawr, PA, USA

    • Martin Phillips

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The authors declare no competing interests.

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Correspondence to Nicholas W. Lukacs.

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https://doi.org/10.1038/s41385-018-0117-1