Pro-inflammatory cytokine blockade attenuates myeloid expansion in a murine model of rheumatoid arthritis
Year: 2019
Type: article
Abstract: Rheumatoid arthritis (RA) is a debilitating autoimmune disease 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.
Source: Haematologica
Authors: 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. Kuhn, Eric M. Pietras
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,157
Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G133672914, Role of RNA splicing factor U2AF1 in regulating hematopoietic stem cell inflammation responses., G6592575151, G681501327, G6856891856, Pro-inflammatory cytokines in hematopoietic stem cell function, University of Colorado Cancer Center Support Grant, Research Training in Rheumatology, G955115260
OpenAlex ID: W2945652237