Extended Data Fig. 5: UPR and inflammasome signalling and inflammatory cell death of Uba1M41T/y BMDMs.
From: Independent mechanisms of inflammation and myeloid bias in VEXAS syndrome
a, b LDH (a) and IL-1\({\rm{\beta }}\) (b) release from Pam3CSK4-primed BMDMs of indicated genotypes treated with indicated agonists of NLRP3, NLRC4 and AIM2 inflammasomes. Treatment was performed 9 days after electroporation. Bars in a, b represent mean values; error bars represent SEM. Each dot represents a biological replicate (n = 3). P values calculated using unpaired, two-sided t-test. c, Cell death measured over 48 h in BMDMs of indicated genotypes treated with indicated stimuli 9 days after electroporation. d-f, Immunoblots of BMDMs of indicated genotypes treated with Bafilomycin A1 (‘Baf’, 50 nM), Tunicamycin (‘Tm’, 5 μg/mL), and/or PERK inhibitor AMG’44 (10 μM) for indicated lengths of time. g, Cell death measured over 48 h in BMDMs of indicated genotypes and treated with indicated stimuli in presence or absence of AMG’44 (10 μM). h, Immunoblots of BMDMs of indicated genotypes treated with TNF alone or in combination with Birinapant (IAPi) for indicated lengths of time or Tunicamycin for 6 h. All assays were performed 9 days after electroporation. Lines in c, g represent mean values of triplicate wells, with 3 images taken per well for quantification; error bands represent SEM. Results are representative of 2 (c, h) or 3 (a, b, d, e, f, g) independent experiments.
