title: Myeloid skewing in murine autoimmune arthritis occurs in hematopoietic stem and primitive progenitor cells.
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 up-regulate 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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Kwadwo A
authors.initials: KA
authors.lastname: Oduro
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Tan
authors.forename: Chan-Kyu
authors.initials: CK
authors.lastname: Kim
authors.forename: Olga
authors.initials: O
authors.lastname: Lubman
authors.forename: Daved
authors.initials: D
authors.lastname: Fremont
authors.forename: Jason C
authors.initials: JC
authors.lastname: Mills
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Choi
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D038041:Lymphopoiesis; D051379:Mice; D020297:Mice, Congenic; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D038042:Myelopoiesis; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D040501:Calgranulin A; D012333:RNA, Messenger; C086145:S100a8 protein, mouse