Sublingual immunotherapy alters expression of IL-4 and its soluble and membrane-bound receptors

Abstract

Seasonal allergic rhinitis (SAR) is a disease of increasing prevalence, which results from an inappropriate T helper cell, type 2 (Th2) response to pollen. Specific immunotherapy (SIT) involves repeated treatment with small doses of pollen and can result in complete and lasting reversal of SAR. Here, we assayed the key Th2 cytokine, IL-4, and its soluble and membrane-bound receptor in patients with SAR before and after SIT. Using allergen-challenge assays, we found that SIT treatment decreased IL-4 cytokine levels, as previously reported. We also observed a significant decrease in the IL-4 membrane-bound receptor (mIL4R) at the level of both mRNA and protein. SIT treatment resulted in a significant increase in the inhibitory soluble IL-4 receptor (sIL4R). Reciprocal changes in mIL4R and sIL4R were also observed in patient serum. Altered mIL4R and sIL4R is a novel explanation for the positive effects of immunotherapy with potential basic and clinical research implications.

Association between Prediagnostic Allergy-Related Serum Cytokines and Glioma

“…That memIL4RA receptor may participate in glioma progression is suggested by Schwartzbaum et al’s [ 32 ] finding that expression of the memIL4RA receptor in glioblastoma tissue is inversely related to a measure of tumor aggression (CD133). Nestor et al [ 33 ] report that sIL4RA concentration is inversely related to expression of memIL4RA, however, the interpretation of this result in the context of allergy and glioma would depend on whether IL4 was bound to sIL4RA. This literature confirms the complex processes underlying a potential association between IL4, its receptors and glioma risk.…”

Distinct Profiles of Soluble Cytokine Receptors Between B-Cell Vitreoretinal Lymphoma and Uveitis

“…Moreover, sIL-4R, which is generated, either by proteolytic cleavage of their membrane forms or by alternative splicing, is reported as an inhibitor of IL-4, a key regulator for Th2 responses. 53,54 Interleukin-4 can inhibit Th17 cell differentiation and reactivation of committed Th17 cells, suggesting that sIL-4R blocks IL-4 action to elicit Th17 responses in the eyes of patients with uveitis.…”

Potential Involvement of Type I Interferon Signaling in Immunotherapy in Seasonal Allergic Rhinitis

“…It is thought to shift the immune response from an excessive Th2 response to a Th1 response and induce T regular cells (Tregs), which is supported by the findings of decreasing IL-4, IL-5, and IL-13, as well as increasing IL-10 [1]. Increasing levels of IFN γ and decreasing levels of IL4R in response to SIT [3] provide additional support to the theory. The mechanism of tolerance is, however, not fully understood.…”