Interleukin‐9 potentiates the interleukin‐4‐induced immunoglobulin (IgG, IgM and IgE) production by normal human B lymphocytes

Abstract

IgE production by normal peripheral blood lymphocytes (PBL) is known to be triggered upon stimulation by interleukin (IL)-4. In the present study we showed that IL-9, another T cell-derived cytokine, markedly potentiated IgE production induced by suboptimal doses of IL-4, whereas no effect of IL-9 was observed in the absence of IL-4. The potentiating effect of IL-9 appeared to be associated with the increased frequency of IgE-producing cells, as revealed by a specific ELISA-spot assay. Under the same experimental conditions, IL-9 also enhanced the IL-4-induced IgG production but did not elicit IgM production. However, IL-9 did not amplify the IL-4-dependent expression of membrane-bound and soluble low affinity receptor for IgE (CD23). IL-4-induced IgE production was also potentiated by IL-6 but not by tumor necrosis factor-alpha and IL-1 beta. The possibility that the activity of IL-9 was mediated by IL-6 released from accessory cells was excluded by the observations that monocyte depletion did not abolish the effect of IL-9 and that IL-9 was still active on fluorescence-assisted cell sorted CD20+ B lymphocytes co-cultured with irradiated murine EL4 cells. In addition, IL-9 was shown to potentiate the IL-4-induced IgG and IgM production by normal human B lymphocytes preactivated with Staphylococcus aureus Cowan strain. Taken together, these data suggest that IL-9 plays a regulatory role in the IL-4-dependent immunoglobulin production.

IL-9 Promotes but Is Not Necessary for Systemic Anaphylaxis

“…In vitro, IL-9 was shown to synergize with suboptimal doses of IL-4 for the production of IgE and IgG1 by LPS-activated murine B cells (19). In humans, very similar observations were reported with peripheral B cells (20). In vivo, IL-9-transgenic mice showed increased IgE production (17,21), but it is not clear whether IL-9 specifically increases the production of this isotype or whether this reflects a global increase in Ig levels.…”

“…It is therefore possible that both OVA-specific IgG and IgE are responsible for IL-9 enhancement of the sensitization phase of anaphylaxis. This could result from a direct effect of IL-9 on B lymphocytes, because IL-9 was reported to have a modest, but significant, effect on Ig production by purified B cells in vitro (19,20). IL-9 could also indirectly promote Ig production by activating Th cells.…”

Human Vδ2 T cells are a major source of interleukin-9

“…Both mediators might be relevant for the interaction with B cells. Because IL-9 promotes IgE production in B cells (40), Vδ2 T cells might thus contribute to the enhanced IgE production (e.g., by coproducing CXCL13, TNFSF13B, and IL-9) in asthma.…”

Interleukin 9 induces expression of three cytokine signal inhibitors: cytokine-inducible SH2-containing protein, suppressor of cytokine signalling (SOCS)-2 and SOCS-3, but only SOCS-3 overexpression suppresses interleukin 9 signalling

“…In addition, IL-9 protects T-cell lymphomas from dexamethasoneinduced apoptosis [5]. The involvement of IL-9 in asthma has been suggested by genetic studies [6][7][8] and is supported by its effects on IgE production [9], mucus production [10], mast cell differentiation [11], eosinophil activation [12] and bronchial hyper-responsiveness [13,14]. Finally, IL-9 is required for an efficient immune response against intestinal parasites such as Trichuris muris [15].…”