HoLab

Interleukin-22: the hub bridging gut homeostasis and metabolism dlvr.it/TPMPKk #immunology

A 2023 @SciImmunology Review contextualizes advances in CAR T cell #cancer immunotherapy, summarizing studies that explore the impact of metabolic stress on this treatment’s efficacy in the tumor microenvironment. Learn more: scim.ag/8o1 #ScienceMagArchives

Our updated inventory of genes required for #OXPHOS & findings on #mito defects in #Menieres is now out at @CellReports! 🎉 🧫 New galactose #CRISPR screen 🎯 481 genes required for #OXPHOS ⚙️ #FAM136A in IMS proteostasis 👂 Mito defects in #Menieres cell.com/cell-reports/f…

Li, Møller, Ho et al. @unil show how tumor-derived lipids can induce an IL-6–dependent increased glutamine synthesis pathway in cancer-associated fibroblasts, supporting CAFs ability to promote pro-tumorigenic tumor-associated macrophages. hubs.la/Q03xvmfr0

🙏 @manuelansede por el fantástico artículo! 🙏 @annalaura_mstrn & Iñaki Robles-Vera @Teriyaky_852 por liderar el proyecto 🙏coautores que han hecho posible el trabajo 🙏@FundLaCaixa @CaixaResearch principal financiador 🙏 @AgEInves @CienciaGob @ERC_Research apoyo adicional

Microbiota-driven antitumor immunity mediated by dendritic cell migration @Nature nature.com/articles/s4158…

The May 2025 edition of the Ludwig Link is here! Catch up on the latest from Ludwig researchers, including awards, new leadership and a gallery of beautiful (and fascinating) micrographs. Check it out online here bit.ly/3Fo6LJR or download the PDF bit.ly/3Sq6Uze

1/ 🚨 Hot off the press in @NatImmunol: CD4⁺ T cells can license Kupffer cells to rescue dysfunctional CD8⁺ T cells in the liver. Hepatitis B virus (HBV) infection is just the proving ground—this is a paradigm shift in tissue immunity. nature.com/articles/s4159… 🧵(1/11) 2/ Chronic HBV infection was the perfect stress test: intrahepatic CD8⁺ T cells are primed yet quickly stall. How to reignite them has been a major interest of our lab. (2/11) 3/ Pre‑activated helper CD4⁺ T cells solve the puzzle. They skip lymph nodes and head straight to the liver, where they form intimate triads with Kupffer cells (KCs), the resident macrophages patrolling sinusoids. (3/11) 4/ Through CD40L‑CD40 contact, those helpers re‑program KCs—turning tolerant scavengers into potent APC‑like cytokine factories. It’s on‑site immune engineering, not remote coaching. (4/11) 5/ Licensed KCs release a two‑part cocktail: • IL‑12 expands the helper pool • IL‑27 wakes up dysfunctional CD8⁺ T cells, restoring effector molecules and metabolic vigor. (5/11) 6/ Dendritic cells? Dispensable. Secondary lymphoid organs? Surgically removed or pharmacologically blocked—help still flows. Immunity can be fabricated in situright inside the parenchyma. (6/11) 7/ Remove KCs and the circuit collapses; block CD40L or IL‑27 and CD8⁺ T cells relapse into lethargy. The essential loop is: CD4 T cell ➜ KC ➜ IL‑27 ➜CD8 T cell. (7/11) 8/ IL‑27 isn’t just necessary—it’s sufficient. Recombinant IL‑27 revived antiviral CD8⁺ activity in mice and super‑charged HBV‑specific T cells from patients. (8/11) 9/ Why care beyond HBV? Tapping a CD4–IL‑27 axis could be a universal key to re‑arming liver‑resident CD8⁺ T cells against infections and cancer (9/11) 10/ The work reframes “CD4 help”: not a lymph‑node pep talk but an on‑site renovation that overrides local tolerance. Therapeutics that mimic KC licensing could deliver potency where it’s needed and spare the rest of the body. (10/11) 11/ Kudos to Valentina Venzin, Cristian Beccaria, all members of the @IannaconeLab & collaborators for charting this intrahepatic circuit. Expect Kupffer‑cell licensing and IL‑27 to enter conversations on cancer immunotherapy, vaccines and beyond. Thoughts welcome! 🙌 @ImmunoPodcast @profvrr @ERC_Research @EMBO @EMBO_YIP @ArmeniseHarvard @AIRC_it @MyUniSR @SanRaffaeleMI (11/11)