Neutralization of TNF Ameliorates Inflammation Caused by OTULIN Deficiency
(A–J) Measurements from tamoxifen (tx)-treated (arrows) CreERT2-Otulinflox bone marrow chimeras injected with (A–C) anti-TNF neutralizing antibodies (αTNF) (data were pooled from two independent experiments), (D–F) anti-G-CSF-neutralizing antibodies (αG-CSF), (G–I) anti-IL-6-neutralizing antibodies (αIL-6), or isotype control as indicated.
(A, D, and G) Body weight of CreERT2-Otulinflox chimeric mice treated with neutralizing antibodies as indicated.
(B, E, and H) Blood neutrophil counts from CreERT2-Otulinflox chimeric mice treated as indicated.
(C, F, and I) Total number of infiltrating CD11b+Gr-1+ neutrophils in spleen and peritoneal lavage (PL) measured by flow cytometry from CreERT2-Otulinflox chimeric mice treated as indicated.
(J) Heatmap of Luminex multiplex analysis of cytokines and chemokines in serum from terminal bleeds on days 6 or 7 from chimeric mice treated as indicated. Numbers indicate relative change compared to isotype-treated del/flox mice within each experiment. G-CSF levels for αG-CSF and αIL-6 were measured by ELISA. Asterisks (∗) indicate the level of statistical significance.
(K) Model of TNF-driven systemic inflammation and the contributions from different cytokines in OTULIN-deficient mice.
(A–J) Data are presented as mean ± SEM, and n represents number of mice.
See also Figure S3.