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Dr. Dawn Bowdish
@msmacrophage.bsky.social
Professor of Medicine, McMaster University Canada Research Chair of Aging & Immunity Executive Director of the Firestone Institute for Respiratory Health
1.2k followers2.2k following167 posts
DDmsmacrophage.bsky.social

Stem cells with Tet2 mutations could outcompete normal cells in old mice that had lots of TNF but not in TNF knockout mice. The aging inflammatory microenvironment contributes to CHIP! (7/n)

Figure 2. Tet2 mutations increase circulating myeloid cells of old WT but not TNF–/– recipient mice. Circulating myeloid immune populations were compared in young WT, old WT, and old TNF–/– recipient mice. (A-C) Total counts of circulating monocytes (A), Ly6Chigh monocytes (B), and neutrophils (C). (D-F) Total circulating monocytes, neutrophils, and Ly6Chigh monocytes as a proportion of total leukocytes (CD45+ ) cells, respectively. (G) Surface expression of F4/80 on Ly6Chigh monocyte. (H) Intracellular expression of TNF in monocytes after stimulation with lipopolysaccharides. Data are shown as a stacked bar plot, in which orange represents gated CD45.2 Tet2–/– cells and blue represents CD45.1 WT cells. Statistical significance determined by 2-way ANOVA with Tukey multiple comparisons test. Letters in the orange and blue columns denote significant differences (P ≤ .05) in the group means of CD45.2 or CD45.1 alleles, respectively. For all variables with the same letter, the difference b
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DDmsmacrophage.bsky.social

Cool finding- People with newly diagnosed #rheumatoidarthritis have lots of TNF and had low level of Tet2 and other CHIP mutants that went down as they started anti-TNF or anti-inflammatory therapy! Proof this happens in humans too (8/n)

Figure 4. CH clones, including mutant TET2, become undetectable in the peripheral blood of older adults administered the TNF blocker, HUMIRA (adalimumab). Mutant-TET2, ASXL1, TP53, CBL, PPM1D, PHF6, and STAG2 clones identified in the peripheral whole blood of patients with RA before any immunomodulatory treatment (baseline) and at 3 and 6 months after treatment with the adalimumab (V1 and V2, respectively), show a significant reduction in CH clones after treatment. (A-B) Mean ± standard error of the mean (A) and detected mutant clones (B) shown. nd, none detected; V1, visit 1; V2, visit 2.
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DD
Dr. Dawn Bowdish
@msmacrophage.bsky.social
Professor of Medicine, McMaster University Canada Research Chair of Aging & Immunity Executive Director of the Firestone Institute for Respiratory Health
1.2k followers2.2k following167 posts
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