Figure 3.

The functional effect of FcεRIβ antisense oligonucleotide (AON) treatment on mast cell activation. Blue arrows represent the path of full-length (FL) MS4A2 and FcεRIβ; red arrows represent the path of truncated (t)-MS4A2 and t-FcεRIβ, as a consequence of FcεRIβ exon skipping by FcεRIβ AONs. (A) MS4A2 pre-mRNA molecule undergoes normal splicing, resulting in transcription of FL-MS4A2 and translation of FcεRIβ. (B) In the presence of FcεRIβ AONs, exon 3 of MS4A2 pre-mRNA molecule is alternatively spliced, resulting in a truncated mature mRNA molecule, t-MS4A2. (C) FL-FcεRIβ forms complex with α and γ-subunits and traffics the receptor complex to the cell surface. (D) At the cell surface, FL-FcεRIβ stabilizes the receptor, enabling activation of FcεRI by antigen via crosslinking IgE antibodies, and subsequent proinflammatory cellular outcomes. (E) In contrast, t-MS4A2 is translated into t-FcεRIβ that lacks the first two transmembrane regions, rendering it incapable of trafficking FcεRIα to the plasma membrane.