Study Identifies Altered Immune Receptor Expression on Blood-Forming Cells in Rheumatoid Arthritis Model
Researchers using a mouse model of rheumatoid arthritis found that key immune receptors — including TREM1, PD-L1, TLR2, and CD14 — are significantly upregulated on hematopoietic stem and progenitor cells (HSPCs) during chronic inflammation. HSPCs are the source of hundreds of billions of new blood and immune cells daily, and their receptor expression normally helps them sense inflammatory signals. The findings suggest that chronic inflammation may reprogram these stem cells in ways that alter immune cell production, potentially driving or sustaining inflammatory disease.
A study posted to bioRxiv examined how chronic inflammation in a murine rheumatoid arthritis model affects the expression of immune receptors on hematopoietic stem and progenitor cells (HSPCs). The researchers found elevated levels of microbial sensors TLR2 and CD14, the orphan inflammatory receptor TREM1, and the immune checkpoint receptor PD-L1 on HSPCs — particularly on myeloid progenitor cells — in arthritic mice compared to healthy controls. When these receptors were stimulated in cell culture, the dynamics of HSPC expansion and differentiation changed significantly, and the responses differed between cells from arthritic and healthy mice. This points to a mechanism by which chronic inflammation could alter the quantity and functional properties of immune cells produced by HSPCs, rather than only acting on mature immune cells. The authors hypothesize that HSPCs may act as central players in the pathogenic inflammatory cycle of rheumatoid arthritis and potentially other chronic inflammatory conditions. The work is a preprint and has not yet undergone peer review.
What's missing
The study is a preprint and has not been peer-reviewed. All experiments were conducted in a mouse model; whether these receptor changes occur similarly in human rheumatoid arthritis patients remains to be demonstrated. The study does not establish whether the observed HSPC reprogramming is a cause or consequence of disease progression, nor does it test therapeutic interventions targeting these receptors. Long-term functional consequences of altered HSPC differentiation on disease outcomes were not assessed.
What different sources said
- bioRxivCenter
Increased Expression and Altered Functional Activities of Immune Receptors TREM1, PD-L1, and Others on Hematopoietic Progenitor Cells in a Mouse Model of Rheumatoid Arthritis
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