Iannacone Lab

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)

Pleased to have contributed to this new @ScienceMagazine paper on how lymphoid tissue chemokines limit CD8⁺ T cell priming duration to preserve T cell functionality. Congrats to @LukasAltenburg2 and Jens Stein! science.org/doi/10.1126/sc…

Review @NatRevImmunol @Kubes_Lab @FGinhoux @iannaconelab Kupffer cells in liver homeostasis and disease: from immune sentinels to metabolic gatekeepers nature.com/articles/s4157…

Great fun to write this review on Kupffer cells with @FGinhoux and @Kubes_Lab, covering origin, diversity and roles in immunity and metabolism, now out @NatRevImmunol. Huge credit to Bruna Araujo David, @frarro1 and Camille Blériot for driving this work. rdcu.be/fckoZ

Abortive infection: T cells as early, antibody-independent defenders dlvr.it/TRrTjj

@Lo_Zanzi @NatRevImmunol Thanks for sharing Ivan!

More than #NeutralizingAntibodies against virus infections!! Check it out @NatRevImmunol by @iannaconelab & friends! 👇👇👇

This calls for a shift in vaccine design: • target early, conserved viral proteins • build tissue-resident immunity • combine antibodies and T cells Great collaboration with Leo Swadling, @ValeFuma91 and @maini_lab

Implications: • T cells can act at inception, not just during clearance • Standard readouts (serology/PCR) miss these events • True exposure and immunity are likely underestimated → We need to measure what T cells actually do

Neutralizing antibodies are not the whole story. In @NatRevImmunol, we highlight an alternative mode of protection: T cells can eliminate infection at its earliest stage, before it becomes detectable. We term this “abortive infection” rdcu.be/fbq8p Thread 1/4

@SabanLab Great work! Congrats Dan 🔥

We are excited to share that our team's paper is published in Immunity: "Resident tissue macrophages maintain intraocular pressure homeostasis." This work grew out of a collaboration between glaucoma clinician-scientist Katy Liu MD PhD, glaucoma physiologist W. Daniel Stamer PhD, and immunologist Daniel Saban PhD, bringing together clinical, physiological, and immunological expertise to tackle a long-standing question: does the immune system directly regulate intraocular pressure? The answer is yes. authors.elsevier.com/a/1mkeB3qNrV3V… #Glaucoma #Immunology #ResidentMacrophages #Ophthalmology #Immunity #CellPress cell.com/immunity/fullt…

Excited to organize @KeystoneSymp Tissue and Spatial Immunology with @LeilaAkkari1 and Hai Qi in February 2027! Join us to explore emerging research in Banff! keysym.us/KSSpatialImmun… #KSSpatialImmune27 pic.x.com/UmTB6SW1x7

Join us for the 2026 GRC Immunochemistry and Immunonbiology "Immune Circuitry and Molecular Pathways in Tissue Homeostasis, Infection, and Disease" in beautiful Barcelona. June 28 - July 3, 2026. Great lineup of speakers! grc.org/immunochemistr…

Don't miss the 2026 @globalimmuno talks!

Great story from the @NieswandtLab in @ScienceMagazine: uncovering a non-classical platelet mechanism that drives inflammation via integrin- and tetraspanin-rich tethers. A fresh angle on thrombo-inflammation. Happy to be part of this work! science.org/doi/10.1126/sc…

@SabanLab Congrats Dan!!

Preprint of National Eye Institute, U01-Funded Consortium Consensus on Ocular Surface Innervation is out ! "Corneal Innervation Research at a Crossroads: A Tool-Driven Roadmap for the Future "

Very clever approach in this must-read paper from @IdoAmitLab! 🔥

Thanks to Chiara Perucchini and Chiara Vespari for their critical contribution

1/ New from our lab 🧪 ARTC2 blockade is widely used to protect tissue Tregs — but when is it truly essential, and for which subsets? 2/ In this @EurJImmunol update, we dissect the subset-specific and context-dependent effects of ARTC2 blockade on hepatic Treg recovery. 3/ At steady state, ARTC2 blockade has a selective benefit: it markedly improves recovery and preserves phenotype of CD44^mid (less-activated) Tregs, while having minimal impact on effector-like eTregs. 4/ During liver inflammation, ARTC2 blockade becomes critical: it boosts overall Treg yield and prevents phenotypic distortion — again with the strongest effect on CD44^mid Tregs. 5/ Key insight: hepatic Treg subsets are not equally sensitive to ARTC2–P2RX7 activation. Less-activated, tissue-resident Tregs are preferentially lost or skewed without protection. 6/ Practical takeaway 💡 • Studying activated/eTregs at steady state? ARTC2 blockade may be optional. • Profiling CD44^mid Tregs or working in inflammatory settings? ARTC2 blockade is essential. 7/ Bottom line: this work reframes ARTC2 blockade from a default reagent to a rational, cost-effective experimental choice. 8/ Proud of the team — led by @CaitlinAAbbott, with @VioletteMouro and colleagues — for turning a technical challenge into actionable guidance for the field. 9/ Read the paper here 👉 onlinelibrary.wiley.com/doi/10.1002/ej… And stay tuned — exciting new discoveries on liver Tregs are coming soon 👀🧬

Thrilled to contribute to this landmark consensus effort led by @Masopust_Vezys and @rafiahmed_lab. A major step toward clearer, shared T cell nomenclature for the field.

Honoured to see our @NatImmunol study highlighted in a thoughtful @JHepatology commentary on the IL-27/Kupffer cell axis in chronic HBV. A great summary of why local tissue immunity matters — and wonderful to see the field engaging with our work. Paper: nature.com/articles/s4159… Commentary: journal-of-hepatology.eu/article/S0168-…