Defective production of soluble HLA-G molecules by peripheral blood monocytes in patients with asthma

Abstract

HLA-G, a human nonclassic MHC class I molecule, is responsible for complex immunoinhibitory functions. HLA-G is expressed as membrane-bound and is secreted as soluble molecules by the peripheral blood CD14+ monocytes activated by IL-10. It has been reported that LPS stimulation induces IL-10 production by PBMCs and that IL-10 levels are reduced in patients with severe asthma compared with patients with mild asthma and healthy subjects. The study was designed to investigate whether this impaired IL-10 production can affect the expression and the secretion of soluble HLA-G (sHLA-G)-1/HLA-G5 molecules. We investigated the production of sHLA-G1/HLA-G5 and IL-10 by specific ELISAs in the culture supernatants of LPS-activated PBMCs from 24 healthy subjects and 20 patients with moderate to severe persistent asthma. LPS stimulation induced the secretion of IL-10 and sHLA-G1/HLA-G5 molecules in all healthy subjects, whereas in patients with asthma, the levels of IL-10 were significantly lower (P < .001) and the number of cultures exhibiting detectable sHLA-G1/HLA-G5 was reduced (7/20; P < .001). The addition of exogenous IL-10 to LPS-stimulated PBMCs from patients with asthma restored normal sHLA-G1/HLA-G5 production. Our data suggest that a specific deficit of IL-10 secretion in patients with asthma could prevent the normal production of sHLA-G1/HLA-G5 molecules. The reduction of immunosuppressive activity mediated by HLA-G could in turn contribute to the persistence of chronic airway inflammation in asthma.