Epithelial Cell Regulation of Type 2 Cytokine Release by Peripheral Blood Mononuclear Cells
Southern A., Gondrand A., Layzell S., Cane JL., Pavord ID., Powell TJ.
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Type 2 cytokines such as IL-13 and IL-5 are important drivers of pathophysiology and exacerbation in asthma. Defining how these type 2 cytokine responses are regulated is a research priority. Epithelial cells promote type 2 responses by releasing alarmins including IL-25, IL-33 and TSLP, but much less is known about inhibitory factors.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>IL-13 release was measured from peripheral blood mononuclear cells (PBMC) cultured with Interleukin (IL)-2 for five days. Epithelial cell lines or human bronchial epithelial cells (HBEC) isolated from healthy or asthma donors were added to these PBMC cultured with IL-2 and release of IL-13 or IL-5 measured. To characterise the mechanisms, we assessed the effect of mechanical disruption of epithelial cells, addition of the COX inhibitor indomethacin and the G-protein inhibitor pertussis toxin.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>PBMC cultured with IL-2 secreted type 2 cytokines in a cell number and time dependent manner. Epithelial cell lines inhibited IL-13 and IL-5 release after co-culture with PBMC in the presence of IL-2, directly, across a transwell and using epithelial cell supernatant. Cells or supernatant from HBEC from healthy or asthma donors also inhibited the cytokine release. Trypsin treatment of conditioned media indicated that inhibitory factor(s) are trypsin insensitive. Mechanical disruption of epithelial cells or indomethacin treatment had no effect, but pertussis toxin reduced epithelial cell inhibition of IL-2 driven type 2 cytokine release.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Epithelial cells regulate cytokine release by soluble factor(s) and this could be an important immunoregulatory function of the airway epithelium.</jats:p></jats:sec>