Identification of the human eosinophil lineage-committed progenitor: Revision of phenotypic definition of the human common myeloid progenitor

Yasuo Mori, Hiromi Iwasaki, Kentaro Kohno, Goichi Yoshimoto, Yoshikane Kikushige, Aki Okeda, Naokuni Uike, Hiroaki Niiro, Katsuto Takenaka, Koji Nagafuji, Toshihiro Miyamoto, Mine Harada, Kiyoshi Takatsu, Koichi Akashi

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

To establish effective therapeutic strategies for eosinophil-related disorders, it is critical to understand the developmental pathway of human eosinophils. In mouse hematopoiesis, eosinophils originate from the eosinophil lineage-committed progenitor (EoP) that has been purified downstream of the granulocyte/macrophage progenitor (GMP). We show that the EoP is also isolatable in human adult bone marrow. The previously defined human common myeloid progenitor (hCMP) population (Manz, M.G., T. Miyamoto, K. Akashi, and I.L. Weissman. 2002. Proc. Natl. Acad. Sci. USA. 99:11872-11877) was composed of the interleukin 5 receptor α chain+ (IL-5Rα +) and IL-5Rα - fractions, and the former was the hEoP. The IL- 5Rα +CD34 +CD38 +IL-3Rα +CD45RA~ hEoPs gave rise exclusively to pure eosinophil colonies but never differentiated into basophils or neutrophils. The IL-5Rα - hCMP generated the hEoP together with the hGMP or the human megakaryocyte/erythrocyte progenitor (hMEP), whereas hGMPs or hMEPs never differentiated into eosinophils. Importantly, the number of hEoPs increased up to 20% of the conventional hCMP population in the bone marrow of patients with eosinophilia, suggesting that the hEoP stage is involved in eosinophil differentiation and expansion in vivo. Accordingly, the phenotypic definition of hCMP should be revised to exclude the hEoP; an "IL-5Rα- negative" criterion should be added to define more homogenous hCMP. The newly identified hEoP is a powerful tool in studying pathogenesis of eosinophilia and could be a therapeutic target for a variety of eosinophil-related disorders.

Original languageEnglish
Pages (from-to)183-193
Number of pages11
JournalJournal of Experimental Medicine
Volume206
Issue number1
DOIs
Publication statusPublished - Jan 16 2009

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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