@GeorgGasteiger
We have an attractive opening for a tenure-track professorship in Single-Cell Systems Biology. Excellent package and infrastructure at the Institute of Systems Immunology @Wue_SI. Great place to live and work in the heart of the franconian wine region!View quoted post on X
jobs.sciencecareers.org/job/673667/jun…
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)View quoted post on X
Excited to share our new paper in @JExpMed 🎉 We show that NK cells use autocrine TGF-β1 signalling to establish tissue residency, form a highly cytotoxic subset, and protect the tissue against viral persistence. rupress.org/jem/article/22…View quoted post on X
