- Eosinophil-derived IL-4 drives heart failure
Diny et al. report a pathogenic role for eosinophils in autoimmune myocarditis and dilated cardiomyopathy. Eosinophils are required for progression of myocarditis to dilated cardiomyopathy and drive severe disease when present in large numbers. Activated cardiac eosinophils mediate this process through IL-4.
- PD-L1 on tumor cells suppresses intratumoral CTLs
Both tumor- and host-derived PD-L1 can play critical roles in immunosuppression; differences in tumor immunogenicity appear to underlie their relative contributions. Juneja et al. show that in immunogenic MC38 tumors, PD-L1 on tumor cells dominates in suppressing tumor immunity by inhibiting CD8 T cell cytotoxicity.
- Complement receptor 3 regulates brain Aβ turnover
Czirr et al. report that microglia lacking complement receptor 3 display increased extracellular Aβ degrading activity and that targeting the receptor with a small molecule increases Aβ clearance in vivo, thus identifying a microglial receptor as a novel therapeutic target.
- Neuropilin 1 in VEGF-induced vascular permeability
Fantin et al. show that the VEGF isoform VEGF165 signals through a complex of VEGFR2 and NRP1, in which the NRP1 cytoplasmic domain promotes the ABL-mediated activation of SRC family kinases to evoke a hyperpermeability response, a known cause of pathological edema.
- Multiple uracil-repair pathways for A-T SHM
Girelli Zubani et al. show that the Pms2 component of the mismatch repair complex and multiple uracil glycosylases contribute, each with a distinct strand bias, to enlarge the Ig gene mutation spectrum from G-C to A-T bases.
- Cullin 3 is required for STAT3 phosphorylation
Li et al. show that OGT-mediated STAT3 O-GlcNAcylation, which is modulated by CUL3-Nrf2 signaling, negatively regulates STAT3 phosphorylation and IL-10 production in macrophages and exacerbates experimental colitis and colitis-associated cancer.
- AKR1B1 regulates EMT in BLBC
The treatment of BLBC represents an unmet medical need. Wu et al. show that AKR1B1 facilitates BLBC progression through a positive feedback loop that activates the EMT program, suggesting that inhibition of AKR1B1 has the potential to become a valuable therapeutic strategy for BLBC.