1. Sign our petition calling on Cochrane to withdraw their review of Exercise Therapy for CFS here.
    Dismiss Notice
  2. Guest, the 'News in Brief' for the week beginning 20th November 2023 is here.
    Dismiss Notice
  3. Welcome! To read the Core Purpose and Values of our forum, click here.
    Dismiss Notice

[Preprint] Trained immunity in human monocyte enhances myeloid-T-cell pathogenic crosstalk in Ankylosing Spondylitis, 2023, Zhao et al.

Discussion in 'Other specific illnesses' started by SNT Gatchaman, Jun 11, 2023.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

    Aotearoa New Zealand
    Trained immunity in human monocyte enhances myeloid-T-cell pathogenic crosstalk in Ankylosing Spondylitis
    Jinyi Zhao; Feng Liu; Claudia Worth; Davide Simone; Frank Penkava; Hui Shi; Jiaqi Li; Shristi Lama; Hai Fang; Jeong Seok Lee; Tae-Jong Kim; Lihua Duan; Paul Bowness; Liye Chen

    Recent studies in infectious, cardiovascular and neurodegenerative diseases have established the presence of memory in innate immune cells. This trained immunity (TI) leads to an enhanced response to a second challenge. Monocytes in Ankylosing Spondylitis (AS), a common form of inflammatory arthritis, are known to be hyper-responsive to microbial stimulus lipopolysaccharide (LPS).

    We asked if TI is present in AS monocytes and, if so, how it contributes to disease pathology. Using Single-cell RNA sequencing (scRNA-seq), flow cytometry and enzyme-linked immunosorbent assays (ELISA), we identify a subset of monocytes from AS patients exhibiting features of trained immunity and being hyperresponsive to LPS stimulation. Surprisingly, both trained monocytes in AS and β-glucan-trained monocytes from healthy donors are hyper-responsive to T-cell-induced activation. scRNA-seq of AS synovial mononuclear cells shows enrichment of a monocyte population with these/analogous features. Additionally, T cell-stimulated monocytes act back on T-cells to support Th17 responses (of established pathology in AS). Lastly, using genetic and chemical perturbations we show that ERN1, an AS risk gene enriched in this trained monocyte population, contributes to T-cell-induced monocyte activation.

    Our data provide strong evidence for the first time for the key role of TI in common human inflammatory arthritis.

    Link | PDF (Preprint: BioRxiv)

Share This Page