@article{400f96d71b014c8db0bc306ac3d0598c,
title = "Pro-inflammatory cytokine blockade attenuates myeloid expansion in a murine model of rheumatoid arthritis",
abstract = "Rcharacterized by chronic inflammation and progressive destruction of joint tissue. It is also characterized by aberrant blood phenotypes including anemia and suppressed lymphopoiesis that contribute to morbidity in RA patients. However, the impact of RA on hematopoietic stem cells (HSC) has not been fully elucidated. Using a collagen-induced mouse model of human RA, we identified systemic inflammation and myeloid overproduction associated with activation of a myeloid differentiation gene program in HSC. Surprisingly, despite ongoing inflammation, HSC from arthritic mice remain in a quiescent state associated with activation of a proliferation arrest gene program. Strikingly, we found that inflammatory cytokine blockade using the interleukin-1 receptor antagonist anakinra led to an attenuation of inflammatory arthritis and myeloid expansion in the bone marrow of arthritic mice. In addition, anakinra reduced expression of inflammation-driven myeloid lineage and proliferation arrest gene programs in HSC of arthritic mice. Altogether, our findings show that inflammatory cytokine blockade can contribute to normalization of hematopoiesis in the context of chronic autoimmune arthritis.",
author = "Giovanny Hernandez and Mills, {Taylor S.} and Rabe, {Jennifer L.} and Chavez, {James S.} and Susan Kuldanek and Gregory Kirkpatrick and Leila Noetzli and Jubair, {Widian K.} and Michelle Zanche and Myers, {Jason R.} and Stevens, {Brett M.} and Fleenor, {Courtney J.} and Biniam Adane and Dinarello, {Charles A.} and John Ashton and Jordan, {Craig T.} and Paola, {Jorge Di} and Hagman, {James R.} and {Michael Holers}, V. and Kuhn, {Kristine A.} and Pietras, {Eric M.}",
note = "Funding Information: The authors would like to thank Phillip Bendele, Shannon Spiegel, Kyle Rothermel and Connor Ohlsen for expert technical assistance. This work was supported by K01 DK098315, R01 DK119394 (to EMP), the Cleo Meador and George Ryland Scott Chair of Medicine in Hematology (to EMP), the Boettcher Foundation Webb-Waring Early Career Investigator Award (to EMP and KAK), F31 HL138754 (to JLR), an NIH Institutional National Service Award 2T32 AI07449 (to CJF), a National Science Foundation Predoctoral Research Fellowship (to TSM), R01 AI098417 (to JRH), and R01 AR51749 (to VMH). This work was also supported in part by the University of Colorado Cancer Center Flow Cytometry Shared Resource, funded by NCI grant P30 CA046934. Publisher Copyright: {\textcopyright}2020 Ferrata Storti Foundation",
year = "2020",
month = mar,
day = "1",
doi = "10.3324/haematol.2018.197210",
language = "English",
volume = "105",
pages = "585--597",
journal = "Haematologica",
issn = "0390-6078",
number = "3",
}