IL-9 Production by Peripheral Blood Mononuclear Cells of Atopic Asthmatics

Abstract

Background: IL-9 might play a critical role in pathogenesis and development of atopic asthma, but there are few reports on allergen-specific IL-9 production by peripheral blood mononuclear cells (PBMCs) obtained from adult asthmatics. Methods: PBMCs were obtained from adult atopic asthmatics and incubated with Dermatophagoides farinae(Der f) extract for the designated time periods. The resulting supernatants were assayed for IL-9 by specific sandwich ELISA. Results: IL-9 production was detectable on day 2 and reached maximum on day 6 after stimulation of PBMCs with Der f extract. IL-9 production in response to Der f extract increased in a dose-dependent manner. CD2- or CD4-bearing cell depletion completely abolished IL-9 production by PBMCs, while CD8-bearing cell depletion did not affect it. Conclusion: CD4+ lymphocytes are the principal source of IL-9 produced by PBMCs of adult atopic asthmatics.

Differentiation, Regulation and Function of Th9 Cells

“…High level of IL-9 production can be detected from the presensitized cells isolated from the peripheral blood of atopic infants when challenged with house dust mite or cat allergen in vitro [89]. Similar response can be detected in peripheral blood mononuclear cells (PBMCs), which are obtained from adult atopic asthmatics and incubated with Dermatophagoides farina (Der f) extract [78].…”

“…It is reported that TGF-β reprograms Th2 cells to lose their characteristic profile and switch to IL-9-secreting cells [82]. Meanwhile, it is of great note that, unlike the observation in vitro, a considerable portion of Th9 cells acquire Th1 cell phenotype and produce Th1 type cytokine, IFN-γ in vivo [76,78]. This phenomenon may be due to multiple environmental signals including the local cytokine milieu in disease models and organs, shaping Th9 cell phenotype to improve and facilitate local adaptive immunity.…”

“…However, it is of great importance that Th9 cells generated from the activation of either antibodies or specific antigens presented by APCs express remarkable phenotypes [76,78].…”

“…Tan et al demonstrates that when stimulation with cytokine milieu specific for Th1 or Th17, Th9 cells shows low level of phenotype change, in contrast with a high level phenotype switching from Th9 to Th2 phenotype [76,78]. It is reported that TGF-β reprograms Th2 cells to lose their characteristic profile and switch to IL-9-secreting cells [82].…”

“…Likewise, Th9 cells produce IL-9, IL-10, and IL-21, even though the roles of IL-10 and IL-21 in Th9 cells function is not clear [13,30,76,78]. Hence, in the following review of Th9 functions, we will focus on the biological functions of IL-9 in immune system as well as the physiological and pathophysiological functions of Th9 cells (Fig.…”