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Can we treat chronic inflammatory arthritis by modulating the abnormal activity of the immune system factory - the bone marrow - to weaken the excessive accumulation of tissue-destructive white blood cells in the joints?

Chronic inflammatory arthritis is characterised by abnormal accumulation of tissue-toxic white blood cells (called neutrophils and macrophages), which cause progressive cartilage and bone destruction. However, the regulation of their production in the bone marrow during inflammation is unknown, impairing our understanding of the mechanisms that lead to chronicity and arthritis aggravation.

We work to improve treatment of rheumatoid arthritis and spondyloarthritis.

Our aim is to understand the molecular and cellular mechanisms that trigger the abnormal activity of the "mother cells" of the blood (the bone marrow stem cells and progenitor cells), in order to identify inflammatory and regulatory molecules that could be targeted to improve therapeutic treatment of rheumatoid arthritis and spondyloarthritis.

The goal of the laboratory is to understand how the activity of haematopoietic stem cells and progenitor cells is regulated during chronic inflammation, using both models of rheumatoid arthritis and spondyloarthritis.

Although substantial progress has been made in identifying the subsets of inflammatory leukocytes that cause joint inflammation, we are still a long way from understanding the complex inflammatory network that leads to self-perpetuation and chronicity of disease, hindering new and more effective drug development.

Inflammatory monocytes/macrophages and neutrophils accumulate in the joints during chronic arthritis, which causes progressive cartilage and bone damage. Peripheral numbers of these short-lived myeloid cells are highly dependent on the bone marrow output, however little is know about the regulation of haematopoietic stem and progenitor cells (HSPC) during chronic inflammation. Importantly, recent studies in anti-microbial immunity showed that HSPC are more reactive to environmental cues than previously anticipated, e.g. to TLR stimuli, IFNs, IL-1 and TNF (reviewed in 1).

Our work is building on Dr Griseri's recent findings in models of chronic intestinal inflammation showing that haematopoiesis was severely dysregulated in the bone marrow during colitis and that highly proliferative granulocyte-monocyte progenitors (GMP) accumulated in the periphery, i.e. spleen and inflamed intestine (see 2 and schematic above).


Bringing together the fields of immunology and haematopoiesis in order to provide a platform for the identification of novel therapeutic targets, our objectives are to elucidate:

  1. How the HSPC compartment adapts to ongoing inflammation and participates in the pathophysiological network in arthritis; 
  2. What are the key targetable inflammatory pathways promoting dysregulated HSPC activity during arthritis; 
  3. Whether the regulatory pathways that normally promote a balanced haematopoiesis and prevent overreaction of HSPCs to environmental cues are deficient during arthritis.

Furthermore, we are interested in investigating the possible crosstalk between intestinal and joint inflammation and its influence on haematopoiesis, as in addition to the joints, the gut is frequently inflamed in spondyloarthritis, e.g. in ankylosing spondylitis.


  1. Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. King KY, Goodell MA. Nat Rev Immunol. 2011;11(10):685-92. 
  2. Dysregulated hematopoietic stem and progenitor cell activity promotes interleukin-23-driven chronic intestinal inflammation. Griseri T, McKenzie BS, Schiering C, Powrie F. Immunity. 2012; 37(6):116-29.

Selected publications