2. Academic Validation
  3. Eosinophil-derived CCL-6 impairs hematopoietic stem cell homeostasis

Eosinophil-derived CCL-6 impairs hematopoietic stem cell homeostasis

  • Cell Res. 2018 Mar;28(3):323-335. doi: 10.1038/cr.2018.2.
Chao Zhang 1,  Weiwei Yi 2,  Fei Li 1,  Xufei Du 1,  Hu Wang 2 3,  Ping Wu 4,  Chao Peng 4,  Man Luo 1,  Wen Hua 1,  Catherine Cl Wong 4,  James J Lee 5,  Wen Li 1,  Zhihua Chen 1,  Songmin Ying 1 6 7,  Zhenyu Ju 2 3,  Huahao Shen 1 8
Affiliations

Affiliations

  • 1 Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Institute of Respiratory Diseases, Hangzhou, Zhejiang 310009, China.
  • 2 Institute of Aging Research, Leibniz Link Partner Group on Stem Cell Aging, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang 310036, China.
  • 3 Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, Guangdong 510632, China.
  • 4 National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China.
  • 5 Department of Biochemistry and Molecular Biology, Mayo Clinic in Arizona, Scottsdale, Arizona 85259, USA.
  • 6 Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
  • 7 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • 8 State Key Lab of Respiratory Disease, Guangzhou, Guangdong 510120, China.
PMID: 29327730 DOI: 10.1038/cr.2018.2
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.

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