Effect of vitamin D on T-helper type 9 polarized human memory cells in chronic persistent asthma

Abstract

BackgroundVitamin D suppresses inflammation and vitamin D deficiency is linked to the severity of asthma symptoms. T-helper type 9 (TH9) cells are important in the pathogenesis, yet the effects of vitamin D on this subset of inflammatory T-helper cells from patients with chronic asthma is unknown. ObjectiveTo determine the effects of vitamin D and dexamethasone on TH9 memory cells from adults with chronic persistent asthma and on a recall response to dust mite allergen. MethodsT-helper memory cells were cultured with cytokines that drive TH9 polarization with vitamin D and/or dexamethasone. Peripheral blood mononuclear cells (PBMCs) from patients with radioallergosorbent test results for house dust mite were stimulated with allergen in the presence or absence of vitamin D. Intracellular cytokines, transcription factors, and identification of cell surface phenotypic markers were determined by flow cytometry. ResultsVitamin D decreased interleukin (IL)-9, IL-5, and IL-8 but increased IL-13+ cells in TH9 cultures. Transcription factors PU.1 and interferon regulatory factor 4 were downregulated by vitamin D but not GATA3 and c-MAF. When PBMCs from patients with positive radioallergosorbent test results were stimulated with dust mite allergen, vitamin D decreased IL-9, IL-5, and IL-13 in T-helper cells (CD4+). TH9 cells present in a recall response were classically TH2 (CD294+), and polarization by transforming growth factor-β and IL-4 altered that phenotype. ConclusionVitamin D decreased inflammatory cytokine profiles in TH9 memory cells and CD4+ cells stimulated with dust mite allergen. Vitamin D is additive with dexamethasone in decreasing inflammatory cytokine production from T-cell subsets implicated in asthma.