Systemic lupus erythematosus (SLE) is an autoimmune disease with significant morbidity and mortality. Type I interferon (IFN) drives SLE pathology and plasmacytoid dendritic cells (pDCs) are potent producers of IFN; however, the specific effects of pDC depletion have not been demonstrated. We show CD123 was highly expressed on pDCs and the anti-CD123 antibody CSL362 potently depleted pDCs in vitro. CSL362 pre-treatment abrogated the induction of IFNα and IFN-induced gene transcription following stimulation with SLE patient-derived serum or immune complexes. RNA transcripts induced in pDCs by ex vivo stimulation with TLR ligands were reflected in gene expression profiles of SLE blood, and correlated with disease severity. TLR ligand-induced protein production by SLE patient peripheral mononuclear cells was abrogated by CSL362 pre-treatment including proteins over expressed in SLE patient serum. These findings implicate pDCs as key drivers in the cellular activation and production of soluble factors seen in SLE.
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h4>Background: /h4> ACO has been characterized as a kind of clinical disease with overlap symptoms of asthma and COPD. However, little is known of the role of eosinophils and corresponding cytokines and chemokines in ACO patients with different treatment responses. h4>Methods: /h4>: To evaluate factors which associates with different treatment responses in patients with ACO. In the present study, we investigated the eosinophils proportion of peripheral blood from ACO patients with acute exacerbation (AE) after treatment, ACO patients with clinical response (CR) after treatment, and healthy volunteers (HV) by using flow cytometry analysis. The plasma levels of corresponding cytokines and chemokines from the three groups were evaluated by ELISA. h4>Results: /h4>: The results showed that ACO patients that had acute exacerbation have relatively lower eosinophils proportions compared to healthy volunteers but have higher eosinophils inflammation compared with patients with clinical response. The percentage of NK1R+ expression population eosinophils was also decreased. Further analysis revealed ACO patients that had acute exacerbation also have relatively higher plasma levels of cytokines and chemokines compared to patients with clinical response after treatments and healthy volunteers. h4>Conclusion: /h4> ACO patients from AE group have relatively lower eosinophil proportion and NK1R+ expression population eosinophil proportion, but higher plasma levels of cytokines and chemokines. Inhibitors of cytokines and chemokines are likely useful agents for treatment of ACO patients which had acute exacerbations.