Eosinophil-derived CCL-6 impairs hematopoietic stem cell homeostasis

Chao Zhang, Weiwei Yi, Fei Li, Xufei Du, Hu Wang, Ping Wu, Chao Peng, Man Luo, Wen Hua, Catherine C.L. Wong, James J. Lee, Wen Li, Zhihua Chen, Songmin Ying, Zhenyu Ju, Huahao Shen

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Eosinophils (Eos) have been long considered as end-stage effector cells in the hierarchical hematopoietic system. Numerous lines of evidence have suggested that Eos are multifunctional leukocytes with respect to the initiation, propagation and regulation of various inflammatory or immune reactions, especially in allergic diseases. Recent studies have shown that Eos are also required for maintenance of bone marrow plasma cells and differentiation of B cells. However, it remains unclear whether Eos contributes to regulation of hematopoietic stem cell (HSC) homeostasis. Here, we demonstrate that Eos disrupt HSC homeostasis by impairing HSC quiescence and reconstitution ability in wild-type mice following ovalbumin (OVA) challenge and even by causing bone marrow HSC failure and exhaustion in Cd3δ -Il-5 transgenic mice. The impaired maintenance and function of HSCs were associated with Eos-induced redox imbalance (increased oxidative phosphorylation and decreased anti-oxidants levels). More importantly, using mass spectrometry, we determined that CCL-6 is expressed at a high level under eosinophilia. We demonstrate that CCL-6 is Eos-derived and responsible for the impaired HSC homeostasis. Interestingly, blockage of CCL-6 with a specific neutralizing antibody, restored the reconstitution ability of HSCs while exacerbating eosinophilia airway inflammation in OVA-challenged mice. Thus, our study reveals an unexpected function of Eos/CCL-6 in HSC homeostasis.

Original languageEnglish (US)
Pages (from-to)323-335
Number of pages13
JournalCell Research
Volume28
Issue number3
DOIs
StatePublished - Mar 1 2018

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Zhang, C., Yi, W., Li, F., Du, X., Wang, H., Wu, P., Peng, C., Luo, M., Hua, W., Wong, C. C. L., Lee, J. J., Li, W., Chen, Z., Ying, S., Ju, Z., & Shen, H. (2018). Eosinophil-derived CCL-6 impairs hematopoietic stem cell homeostasis. Cell Research, 28(3), 323-335. https://doi.org/10.1038/cr.2018.2