Pro-inflammatory cytokine blockade attenuates myeloid expansion in a murine model of rheumatoid arthritis

Giovanny Hernandez, Taylor S. Mills, Jennifer L. Rabe, James S. Chavez, Susan Kuldanek, Gregory Kirkpatrick, Leila Noetzli, Widian K. Jubair, Michelle Zanche, Jason R. Myers, Brett M. Stevens, Courtney J. Fleenor, Biniam Adane, Charles A. Dinarello, John Ashton, Craig T. Jordan, Jorge Di Paola, James R. Hagman, V. Michael Holers, Kristine A. KuhnEric M. Pietras

Research output: Contribution to journalArticlepeer-review

19 Scopus citations



characterized 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.

Original languageEnglish
Pages (from-to)585-597
Number of pages13
Issue number3
StatePublished - Mar 1 2020


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