Ex Vivo Overoxygenation of Lymphocyte Subpopulations in Fibrosing Hypersensitivity Lung Disease

Ex Vivo overoxygenation of Lymphocyte Subpopulations in Fibrosing Hypersensitivity Lung Disease, attenuated by a Sphingosine-1-Phosphate Receptor Ligand.

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Lymphocytes are central to the pathogenesis of hypersensitivity pneumonitis, and ample evidence supports that lymphocytes are modulated by sphingosine-1-phosphate receptor-modifying drugs. The aim of this exploratory study was to determine whether a pharmacological ligand for sphingosine-1-phosphate receptors interfered with lymphocyte activation obtained from patients with fibrosing hypersensitivity pneumonitis. Peripheral blood mononuclear cells (PBMCs) from 12 patients and 10 control subjects were subjected to CD3/CD28 stimulation, and isolated B lymphocytes were incubated with a TLR9 ligand. We then tested how these stimulations were affected by ozanimod, a sphingosine-1-phosphate receptor ligand. Patient T and B cell subpopulations overexpressed CD69 and cytokines such as TNF and IL-4 in response to CD3/CD28 stimulation, compared with controls. In patients with fibrosing hypersensitivity pneumonitis, ozanimod attenuated CD3/CD28 induction of CD69, IL-4 and TNF in CD8 T cells, but not in CD4 T cells. In isolated B lymphocytes stimulated with TLR9 ligand, ozanimod reduced cell surface expression of CD69, CD86 and CD40, as well as accumulation of TNF and IL-6 in the supernatant. We conclude that lymphocyte subpopulations are functionally impacted in patients with fibrosing hypersensitivity pneumonitis, and that ozanimod can interfere ex vivo with the overoxygenation of B cells and CD8 T cells in response to specific stimuli.

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Read the article here: https: //www.mdpi.com/1422-0067/26/7/3197

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TransBioTech researcher associated with the publication: Carole-Ann Huppé

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