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Haematopoiesis

Osteopontin skews lymphoid–myeloid balance

Nature Reviews Immunology volume 17, page 466 (2017)Cite this article

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The balance between the production of myeloid cells and lymphoid cells in the bone marrow is tightly regulated to adapt to demand. For example, after severe infection, inflammation or irradiation, 'emergency myelopoiesis' compensates for the loss of myeloid cells. This study reports distinct roles for different isoforms of osteopontin (OPN) — secreted (sOPN) and intracellular (iOPN) — that together function to skew the balance of haematopoietic cells towards decreased myeloid cell numbers and increased lymphoid cell numbers.

To investigate how OPN restricts emergency myelopoiesis, the authors showed that Spp1−/− multipotent progenitors express higher levels of Birc5 (which encodes the anti-apoptotic protein survivin) and have increased survival in ex vivo assays compared with wild-type progenitors. In irradiated wild-type host mice receiving wild-type donor cells, there was significantly greater apoptosis of myeloid progenitors (but not lymphoid progenitors) than in mice receiving Spp1−/− donor cells. Thus, OPN promotes apoptosis of myeloid progenitors. By contrast, OPN was shown to be anti-apoptotic for differentiated lymphoid cells during, for example, chronic lymphopenia-induced proliferation of B and T cells. In a T cell-mediated colitis model, disease severity was reduced in mice receiving Spp1−/− donor T cells compared with mice receiving wild-type T cells.

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References

  1. Kanayama, M. et al. Skewing of the population balance of lymphoid and myeloid cells by secreted and intracellular osteopontin. Nat. Immunol. http://dx.doi.org/10.1038/ni.3791, (2017)

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Authors
  1. Kirsty Minton
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Minton, K. Osteopontin skews lymphoid–myeloid balance. Nat Rev Immunol 17, 466 (2017). https://doi.org/10.1038/nri.2017.80

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