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Nat Immunol. 2017 Sep;18(9):973-984. doi: 10.1038/ni.3791. Epub 2017 Jul 3.

Skewing of the population balance of lymphoid and myeloid cells by secreted and intracellular osteopontin.

Author information

1
Department of Immunology, Duke University School of Medicine, Durham, North Carolina, USA.
2
Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA.
3
Department of Neurology, Duke University School of Medicine, Durham, North Carolina, USA.
4
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.

Abstract

The balance of myeloid populations and lymphoid populations must be well controlled. Here we found that osteopontin (OPN) skewed this balance during pathogenic conditions such as infection and autoimmunity. Notably, two isoforms of OPN exerted distinct effects in shifting this balance through cell-type-specific regulation of apoptosis. Intracellular OPN (iOPN) diminished the population size of myeloid progenitor cells and myeloid cells, and secreted OPN (sOPN) increase the population size of lymphoid cells. The total effect of OPN on skewing the leukocyte population balance was observed as host sensitivity to early systemic infection with Candida albicans and T cell-mediated colitis. Our study suggests previously unknown detrimental roles for two OPN isoforms in causing the imbalance of leukocyte populations.

PMID:
28671690
PMCID:
PMC5568448
DOI:
10.1038/ni.3791
[Indexed for MEDLINE]
Free PMC Article

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