Stress granule assembly impairs macrophage efferocytosis to aggravate allergic rhinitis

The assembly of cytoplasmic stress granule (SG) in response to various stress inducers results in the arrest of protein translation and then orchestrates cell fate, which has been demonstrated in the regulation of various physiological and pathological processes. However, the potential role of SG formation in the progression of allergic diseases remains unknown. Here, in the nasal tissues from both allergic rhinitis (AR) mouse models and patients, we found that SGs were assembled specifically in the macrophages within nasal mucosa, which restrained the efferocytotic ability of macrophages and suppressed the clearance of apoptotic immune cells, thus promoting AR progression. Mechanistically, upon stress, intracellular m7G-modified Lrp1 mRNA, a typical efferocytosis receptor, was transported by the m7G reader QKI7 into the assembled SGs of macrophages, which sequestered the translation of Lrp1 mRNA and then inhibited efferocytosis. Inhibition of SG assembly significantly repressed AR progression. Therefore, SG assembly impairs macrophage efferocytosis and aggravates AR, and the inhibition of SGs bears considerable potential in the targeted therapy.