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Osteopontin and the immune system: another brick in the wall

Cellular & Molecular Immunology volume 15, pages 405–407 (2018)Cite this article

The innate and adaptive arms of the immune system are finely tuned to efficiently react to either endogenous or exogenous noxiae that perturb the function of our tissues and organs, thus rapidly returning to homeostasis with minimal collateral damage. The molecular mechanisms by which this occurs have been only partially elucidated. The work by Kanayama et al. 1 contributes to the building of this wall of knowledge by adding an important brick. They show that osteopontin (OPN), a phosphorylated protein of the extracellular matrix (ECM), has a dominant role in balancing lymphoid and myeloid cells during emergency granulopoiesis (that is, an increased cellular output from the bone marrow to meet the acute demand for the respective blood cell type).2 OPN that is produced and released by bone marrow (BM) stromal cells negatively impacts the pool size of hematopoietic stem cells (that is, Lin−Sca-1+c-kit+).3,4 The role of OPN on myeloid and lymphoid progenitor cells was unknown. Kanayama et al. 1 clearly establish that in conditions that trigger emergency granulopoiesis (for example, irradiation, treatment with thioglycollate, C. albicans infection), intracellular OPN (iOPN) limits myeloid progenitor cells by exerting a pro-apoptotic role. While iOPN is not pro-apoptotic in neutrophils, monocytes or lymphoid progenitors, secreted osteopontin (sOPN) favors T- and B-cell expansion by inhibiting apoptosis. Thus, the net effect of OPN consists of decreasing the size of myeloid progenitors and increasing the size of lymphoid cells during demand-adapted myelopoiesis and lymphoid cell expansion in lymphopenic hosts.

The authors started from the observation that in mixed BM chimeras (that is, lethally irradiated wild-type mice reconstituted with a 1:1 ratio of BM cells from OPN+/+ and OPN−/− mice), OPN−/− donor cells had larger myeloid cell populations and smaller lymphoid cell populations than OPN−/− donor cells in the BM, despite similar concentrations of serum OPN in wild-type mice and chimeras. Indeed, multipotent progenitors, common myeloid progenitors (CMPs) and granulocyte–macrophage progenitors (GMPs) were enriched, and common lymphoid progenitors (CLPs) were slightly decreased in the BM from OPN−/− mice, when compared to the BM of OPN+/+ mice. Thus, in irradiated recipient mice, iOPN in hematopoietic progenitor cells, and not sOPN, is responsible for decreasing the pool of myeloid progenitors.

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References

  1. Kanayama M, Xu S, Danzaki K, Gibson JR, Inoue M, Gregory SG et al. Skewing of the population balance of lymphoid and myeloid cells by secreted and intracellular osteopontin. Nat Immunol 2017; 18: 973–984.

    Article  CAS  Google Scholar 

  2. Manz MG, Boettcher S. Emergency granulopoiesis. Nat Rev Immunol 2014; 14: 302–314.

    Article  CAS  Google Scholar 

  3. Stier S, Ko Y, Forkert R, Lutz C, Neuhaus T, Grunewald E et al. Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. J Exp Med 2005; 201: 1781–1791.

    Article  CAS  Google Scholar 

  4. Nilsson SK, Johnston HM, Whitty GA, Williams B, Webb RJ, Denhardt DT et al. Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood 2005; 106: 1232–1239.

    Article  CAS  Google Scholar 

  5. Qin F, Tian J, Zhou D, Chen L. Mst1 and Mst2 kinases: regulations and diseases. Cell Biosci 2013; 3: 31.

    Article  Google Scholar 

  6. Rittling SR, Singh R. Osteopontin in immune-mediated diseases. J Dent Res 2015; 94: 1638–1645.

    Article  CAS  Google Scholar 

  7. Cantor H, Shinohara ML. Regulation of T-helper-cell lineage development by osteopontin: the inside story. Nat Rev Immunol 2009; 9: 137–141.

    Article  CAS  Google Scholar 

  8. Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S et al. Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 2000; 287: 860–864.

    Article  CAS  Google Scholar 

  9. Murugaiyan G, Mittal A, Weiner HL. Increased osteopontin expression in dendritic cells amplifies IL-17 production by CD4+ T cells in experimental autoimmune encephalomyelitis and in multiple sclerosis. J Immunol 2008; 181: 7480–7488.

    Article  CAS  Google Scholar 

  10. Uede T. Osteopontin, intrinsic tissue regulator of intractable inflammatory diseases. Pathol Int 2011; 61: 265–280.

    Article  CAS  Google Scholar 

  11. Heilmann K, Hoffmann U, Witte E, Loddenkemper C, Sina C, Schreiber S et al. Osteopontin as two-sided mediator of intestinal inflammation. J Cell Mol Med 2009; 13: 1162–1174.

    Article  CAS  Google Scholar 

  12. Shevde LA, Samant RS. Role of osteopontin in the pathophysiology of cancer. Matrix Biol 2014; 37: 131–141.

    Article  CAS  Google Scholar 

  13. Sangaletti S, Tripodo C, Sandri S, Torselli I, Vitali C, Ratti C et al. Osteopontin shapes immunosuppression in the metastatic niche. Cancer Res 2014; 74: 4706–4719.

    Article  CAS  Google Scholar 

  14. Jachetti E, Caputo S, Mazzoleni S, Brambillasca CS, Parigi SM, Grioni M et al. Tenascin-C protects cancer stem-like cells from immune surveillance by arresting T-cell activation. Cancer Res 2015; 75: 2095–2108.

    Article  CAS  Google Scholar 

  15. Ruvolo PP. Galectin 3 as a guardian of the tumor microenvironment. Biochim Biophys Acta 2016; 1863: 427–437.

    Article  CAS  Google Scholar 

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Acknowledgements

The work was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC; grant no. IG16807 to MB and FIRC fellowship no. 18314 to SC).

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  1. Cellular Immunology Unit, Department of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132, Milan, Italy

    Sara Caputo & Matteo Bellone

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Correspondence to Matteo Bellone.

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Caputo, S., Bellone, M. Osteopontin and the immune system: another brick in the wall. Cell Mol Immunol 15, 405–407 (2018). https://doi.org/10.1038/cmi.2017.94

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