FcRn alleviates mycobacterium-induced lung injury by triggering YBX1-mediated autophagy.

The neonatal fc receptor (FcRn) is indispensable in sustaining IgG homeostasis. Recently, the potential role of FcRn in infectious diseases has attracted more attention. However, the function of FcRn in tuberculosis is unclear. The present study aimed to investigate the role of FcRn in regulating BCG infection-induced autophagy in vitro and vivo. FCGRT knockout mice and FcRn knockdown cells were constructed by CRISPR/Cas9 and small interfering RNA. The related indicators of autophagy were detected by transmission electron microscopy, flow cytometry, and western blot. The proteins interacting with FcRn were screened by immunoprecipitation (IP) and mass spectrometry (MS). The results showed more lung injury and less autophagy marker expression in the KO-FcRn mice lungs than wild type (WT) mice after BCG infection (p < 0.01). Meanwhile, si-FcRn restrained BCG-induced macrophage autophagy by activating the PI3K/AKT/m-TOR pathway. Furthermore, FcRn was confirmed to interact with the Y-box binding protein 1 (YBX1) and promote its nuclear translocation. Hence, the current study proved that FcRn protects against BCG-induced lung injury by triggering YBX1-mediated autophagy and suppressing the PI3K /AKT/mTOR signaling pathway. These findings present a novel understanding of the immune role of FcRn in treating and preventing tuberculosis.