Expression of Siglec-9 in peripheral blood neutrophils was increased and associated with disease severity in patients with AECOPD.

BACKGROUND: The pathogenesis and treatment strategies for chronic obstructive pulmonary disease (COPD) require further exploration. Abnormal neutrophil inflammation and the overexpression of neutrophil extracellular traps (NETs) are closely associated with acute exacerbations of COPD (AECOPD). Siglec-9, a specific receptor expressed on neutrophils that inhibits their function, prompted us to investigate its relationship with NETs found in induced sputum and the severity of the disease. METHODS: We collected clinical data from patients with AECOPD and assessed the expression of Siglec-9 in peripheral blood neutrophils and the presence of NETs in induced sputum. We then observed the correlation between Siglec-9, the inflammatory response, and the severity of AECOPD. RESULTS: We observed an increase in the expression of Siglec-9 in the peripheral blood neutrophils of patients with AECOPD. Concurrently, these patients exhibited more severe clinical symptoms, higher systemic inflammation levels, and a reduced quality of life compared to those with induced sputum NET expression. Further subgroup analysis of AECOPD patients with high Siglec-9 expression revealed worsened quality of life and more severe inflammation, particularly in indicators such as the BODE index, CRP, peripheral blood neutrophil count, IL-6, IL-8, TNF-α expression, and others. Furthermore, we noted a significant increase in NET-specific expression in the sputum of patients with high Siglec-9 expression levels. In comparison to patients with low Siglec-9 expression, those with high expression experienced more systemic inflammatory reactions and a lower quality of life. Correlation analysis of the aforementioned indicators revealed that the expression ratio of Siglec-9 in the peripheral blood of patients correlated with lung function, quality of life, and NETs in the induced sputum of patients with AECOPD. CONCLUSION: The increased expression of Siglec-9 in peripheral blood neutrophils of AECOPD patients leads to elevated NET expression in induced sputum, exacerbating the systemic inflammatory response and worsening lung function and quality of life in these patients.

Siglec-9 is upregulated in rheumatoid arthritis and suppresses collagen-induced arthritis through reciprocal regulation of Th17-/Treg-cell differentiation.

Sialic acid-binding Ig-like lectin-9 (Siglec-9) is a novel sialic acid-binding member of the immunoglobulin superfamily and is broadly expressed on immune cells, which can inhibit both innate and adaptive immune responses through immunoreceptor tyrosine-based inhibitory motifs. However, the exact role of Siglec-9 in the pathogenesis of rheumatoid arthritis (RA) remains unknown. In this study, we determined soluble Siglec-9 (sSiglec-9) levels in the serum and synovial fluid of patients with RA and evaluated the relation between sSiglec-9 levels and clinical factors. In addition, we investigated whether Siglec-9 could alleviate collagen-induced arthritis (CIA) development in mice and explored the molecular mechanisms involved. The results showed that, in the serum and synovial fluid of patients with RA, sSiglec-9 levels were elevated. Thus, high sSiglec-9 serum levels associated with disease severity in patients with RA. Furthermore, administration of recombinant human Siglec-9 Fc chimera protein significantly attenuated collagen-induced arthritis development in vivo and in vitro by reciprocal regulation of the differentiation of Th17 and Treg cells. Our findings collectively indicate that Siglec-9 plays a potent immunosuppressive role in the pathogenesis of RA by reciprocal regulation of Th17-/Treg-cell differentiation. In conclusion, Siglec-9 may serve as a potential diagnostic and therapeutic target for RA.