Indeed, we screen all severe cocci patients referred to UCLA (rare, yes ~ 2/month) for their Th2 ratio before starting dupilumab. As you'll see in an upcoming JCI Insight paper (!) we defined a threshold Th2/Th1 ratio of >1.27 as a useful cutoff for treatment. It's personalized therapy, indeed!
We have been working on the T cell dysregulation underlying coccidioidomycosis (Valley fever). Following up on our NEJM paper in 2020 (PMID: 32521134), we've now treated 18 patients at UCLA with immunomodulation (dupilumab and/or interferon gamma). We share a new case series doi.org/10.1093/cid/...
Thank you! We believe IL4/13 blockade is helpful for those subjects with disseminated or severe coccidioidomycosis who show abnormal Th2 skewing (Th2 / Th1 ratio by intracellular cytokine staining > controls).
Spin your antibodies at 20k x g for a few minutes immediately before using; keep the antibodies cold; consider adding something like BSA 0.1%
This cool paper builds on the amazing work in hyaluronan and inflammation by @pbollyky.bsky.social's group at Stanford. His team published that a safe, small molecule could block HA synthesis, reduce HA in sputum (PMID: 35499083), and clinically improves lung fibrosis (PMID: 40451287)!
I'm so excited to share our new paper in Cell where we provided T cells two genes that allow metabolism of a safe form of glucose (derived from cellulose). This fuel allows human CAR-T cells to fight tumors better! Congrats go to Matt Miller, now a postdoc at Salk. www.cell.com/cell/fulltex...
Intriguing paper from @josephsunlab.bsky.social about IL12 signaling that comes *before* TCR signaling leading to memory. Re "delayed expression" of IL12R in CD8 T cells, I wonder if that's related to the change from short to full-length transcripts that occurs upon activation (see PMID: 23024274)?
Yay! I'll be there, and speaking on our use of machine learning at UCLA to find undiagnosed patients with immune deficiency diseases.
This is a fantastic article by the @fletcherlabucb.bsky.social at Berkeley about macrophages assessing and eating the cells they bump into based on their membrane tension. I wonder if regulatory T cells, which also perform trogocytosis, use a similar mechanism (not FcγR-based, obviously).
Cool advance in the epigenetics of Lamarckism. I wonder if a recent history of infections in fathers-to-be can be encoded in the epigenetics of sperm and passed down as well (e.g., microRNAs or chromatin organization at interferon response genes after viral infection).
Melissa Lechner's group at UCLA identified both CD4+ (Tfh) and CD8+ (Tc1) T cells as drivers of the autoimmune diabetes that arises after anti-PD1 therapy, and showed the nonspecific JAK inhib ruxolitinib could prevent it! Wow. My suspicion is that targeting IFNg-STAT1 alone probably is enough.
One the many advances in this incredible paper by Columbia's Milner and Izar labs shows that GOF variants in PIK3CD are not all that rare, including p.M285T that occurs in 1/8000, and is correlated with autoimmune diseases. There are many more APDS patients lurking out there! #IEI #raredisease
New antifungals are much needed -- 41 of these patients receiving olorofim had coccidioidomycosis. #valleyfever
⚠️ Effective Monday 2/10/25, NIH indirect rate capped at 15%. Applies to existing & future grants.
—> Deep budget cuts & program closures coming to a university near you.
Is this the break the glass moment for university administrators who have been silent so far about the attack on science?
Bravo to Paul Bollyky @pbollyky.bsky.social at Stanford for his lab's paper showing that complementary groups of phage can be mixed to provide broad and effective antimicrobial therapy against Pseudomonas and Staph infections. Brilliant work!
www.nature.com/articles/s41...
Please add me to your next pack. My lab studies inborn errors of immunity and T cells.
