Hematopoietic stem cell function in rheumatoid arthritis

Inés Colmegna, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalReview articlepeer-review

Abstract

Abnormal innate and adaptive immune responses are critically involved in the pathogenesis of rheumatoid arthritis (RA). Anti-inflammatory and immunosuppressive therapies have been highly successful, but a cure for the disease has remained elusive, mostly due to lack of knowledge of disease instigators and the causative immune system abnormalities. RA is associated with premature aging of the immune system, which has been attributed to the chronic inflammatory milieu. However, recent data draw attention to processes of impaired immune regeneration as an underlying defect. Specifically, bone marrow hematopoietic stem cells (HSCs), permanently regenerating myeloid and lymphoid lineages, are functionally defective in RA, jeopardizing repopulation of the immune system. In RA, the pool of circulating HSCs is contracted and HSCs respond inadequately to hematopoietic growth factors. Most importantly, RA HSCs have age-inappropriate telomeric shortening, indicative of excessive proliferative stress. Defects in HSCs broaden the immunopathogenesis of RA to include early events in the shaping of the immune system. Restoring HSC function will be a necessary step in re-establishing immune health in RA patients.

Original languageEnglish (US)
Pages (from-to)559-569
Number of pages11
JournalFuture Rheumatology
Volume3
Issue number6
DOIs
StatePublished - 2008

Keywords

  • Aging
  • DNA damage
  • HSC
  • Hematopoiesis
  • Hematopoietic stem cells
  • RA
  • Rheumatoid arthritis
  • Senescence
  • Telomerase
  • Telomeres

ASJC Scopus subject areas

  • Rheumatology

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