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

Autor:	Hernandez G; Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO., Mills TS; Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO., Rabe JL; Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO., Chavez JS; Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO., Kuldanek S; Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO., Kirkpatrick G; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO., Noetzli L; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO., Jubair WK; Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO., Zanche M; Genomics Research Center, University of Rochester, Rochester, NY., Myers JR; Genomics Research Center, University of Rochester, Rochester, NY., Stevens BM; Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO., Fleenor CJ; Department of Biomedical Research, National Jewish Health, Denver, CO.; Department of Immunology & Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO., Adane B; Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO., Dinarello CA; Division of Infectious Disease, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Ashton J; Genomics Research Center, University of Rochester, Rochester, NY., Jordan CT; Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO., Di Paola J; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO., Hagman JR; Department of Biomedical Research, National Jewish Health, Denver, CO.; Department of Immunology & Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO., Holers VM; Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO., Kuhn KA; Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO., Pietras EM; Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO eric.pietras@CUAnschutz.edu.; Department of Immunology & Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO.
Jazyk:	angličtina
Zdroj:	Haematologica [Haematologica] 2020 Mar; Vol. 105 (3), pp. 585-597. Date of Electronic Publication: 2019 May 17.
DOI:	10.3324/haematol.2018.197210
Abstrakt:	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. (Copyright© 2020 Ferrata Storti Foundation.)
Databáze:	MEDLINE
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