Myeloid skewing in murine autoimmune arthritis occurs in hematopoietic stem and primitive progenitor cells

Kwadwo A. Oduro, Fang Liu, Qing Tan, Chan Kyu Kim, Olga Lubman, Daved Fremont, Jason C. Mills, Kyunghee Choi

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Skewing toward myeloid cell production is often observed in chronic inflammation and autoimmune diseases. Herein, we determined whether persistent myeloid activation and proinflammatory output occurring in pathologic conditions is at the level of hematopoietic stem and primitive progenitor cells (HSPPCs). By using a mouse arthritis model, we found that even though HSPPCs in arthritis still retained the capacity to differentiate into different lineages, they acquired enhanced in vitro and in vivo propensity in a disease-dependent manner to generate myeloid cells, the key perpetrators of tissue damage in arthritis. This myeloid skewing was cell intrinsic, as arthritic HSPPCs upregulate myeloid-specific transcripts including S100a8. Exogenous S100a8 promoted myeloid cell output from wild-type HSPPCs, suggesting mechanistic involvement of this gene in the myeloid priming that occurs in arthritic HSPPCs. Therefore, our results indicate that in arthritic mice, HSPPCs adopt a pathologic state that favors disease persistence.

Original languageEnglish
Pages (from-to)2203-2213
Number of pages11
JournalBlood
Volume120
Issue number11
DOIs
StatePublished - Sep 13 2012

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