Joanna Groom

Abstract deadline extended to Monday, June 30! And travel grants are still available to student and post-doc members. Don't miss out - REPOST to share the info with others.

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🧠🍔 Just 48 hours on a high-fat diet can weaken gut immunity. Our new study shows saturated fats rapidly impair ILC3s!
Proud to see this featured by
@wehi-research.bsky.social as I continue to explore these questions @monashuniversity.bsky.social with the IMI Lab!

ICYMI: explore our #Immunology collection, highlighting B cells, CD8+ T cell stemness, priming and differentiation, CD4+ T cell heterogeneity, autoimmunity, lymphatic immunophysiology and innate immune signaling. 👉 rupress.org/jem/collecti...
#AAI2025

Congratulations Doug and team

So excited to share our first neuro focused paper from the lab, we show that CXCL4 (PF4) is transported into the brain by proteoglycans within the endothelial glycocalyx and that GAG binding also mediates the pro neurogenesis effects of CXCL4. www.biorxiv.org/content/10.1...

Excited to have our latest research published in @jem.org this week and also highlighted by @natrevimmunol.nature.com
@wehi-research.bsky.social @benjbroom.bsky.social

Thanks to @cytokinesociety.bsky.social Signals+ for highlighting our recent work @benjbroom.bsky.social @wehi-research.bsky.social

Lovely work Isaak. Good to see you here.

#WeekendRead! #InterferonFriendOrFoe!
@benjbroom.bsky.social @groomlab.bsky.social &co show @jem.org that transient type I IFN inhibition upon LCMV infection or a mRNA vaccine boosts stem-like memory CD8 T cells by altering their location within the draining lymph node, potentiating virus protection

Gonna guess immunologists will regret the "precursor of exhausted" T cell name in the future.

Surely we are already there

This journey was over 2.5 since initial submission 😭
led by @benjbroom.bsky.social with support from the whole lab, @chinweetan.bsky.social, WEHI’s Dynamic Imaging Facility, and Norbert and Colin's teams.

⭐️ Our work demonstrate that the formation of effector cells is not needed to obtain potent memory T cell responses.
⭐️ Thus our study suggests a new approach to vaccine design to direct stem cell-like memory CD8+ T cell formation and function.

⭐️ Interplay of type I and II IFNs modify chemokine abundance to position CD8+ T cells within the lymph node. ⭐️This has implications for patients with LOF mutations in IFN-I signaling or auto-IFN-I antibodies.

⭐️ Our study aligns with others (Utzschneider, Ahmed, Zehn) unifying stem-like cells in acute, chronic infections and cancer
⭐️ Suggesting in chronicity the transition to memory is "interrupted"
⭐️ Importantly we reveal markers that allow these states to be tracked in vaccine/immunotherapy responses

Combined:
⭐️ CD8+ T cells primed in the absence of IFN-I signaling transition from Tpex to Tscm cells.
⭐️ These are plastic cellular states, with antigen availability dictating the transition between the two.
⭐️ We propose this natural transition promotes development of potent CD8+ memory formation.

With help from Norbert Pardi @upenn.edu and Colin Pouton @monashuniversity.bsky.social we applied this knowledge to mRNA-LNP vaccination to demonstrate that IFN-I blockade provided protective benefit against subsequent chronic viral infection.

We demonstrated a counterintuitive increase in IFNg which controlled chemokine abundance and cell location. Whenever we observed cell retention within the paracortex, it was associated with increased stem-like CD8+ T cell formation.

We investigated how CXCR3 chemokines guide CD8+ T cell location are regulated.

To our surprise, they were increased when IFN-I signaling was inhibited. Yet, CD8+ T cells were retained in the lymph node paracortex due to receptor desensitization.

Further, we tracked the plasticity of these two cell states, with antigen availability dictating the transition between CD61+ Tpex and CD55+ Tscm cell states.

Overlaying scRNAseq with Totalseq, we could not only define the transcriptional Tpex and Tscm cell signatures, but cell surface markers that tracked conversion between these transient populations.

We looked at this differentiation in detail to show that at day 8 post infection, IFN-I blocked stem-like cells appear similar to Tpex cells seen in chronic infection. After viral clearance, the population resemble Tscm, the transition associated with decreased inhibitory receptor expression.

Wait… doesn’t this just induce chronicity and exhaustion (as demonstrated by the Brooks lab and others)?

The key here is early and transient IFN-I blockade. While delayed, we see total viral clearance with stem-like CD8+ T cell accumulation being distinct from that seen in chronic infection.

We used early, transient blocking of type I interferon (IFN-I) to promote TCF-1+ stem-like CD8+ T cells in the absence of effector CD8+ T cells during acute LCMV infection.

Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands - Nature Immunology T cells are highly dynamic and their spatial and cellular interactions can influence their differentiation program. Groom and colleagues use three-dimensional spatial imaging to show that effector and...

Previously we identified that the lymph node paracortex provided a spatial niche which promotes Tscm cell formation. Here, we proposed this niche protects Tscm cells way from inflammation at the lymph node periphery.
www.nature.com/articles/s41...

TCF-1+ stem-like CD8+ T cells encompass two populations with therapeutic potential:
1. Tscm cells – seen in vaccine and acute infection
2. Tpex cells – seen in chronic infection and cancer

But their developmental relationship and how to individually define or promote them is lacking.

Very excited our work out in @jem.org “Transient inhibition of type I interferon enhances CD8+ T cell stemness and vaccine protection”
@wehi-research.bsky.social led by talented (and determined) PhD student @benjbroom.bsky.social
Thread below.

Transient inhibition of type I IFN enhances CD8+ T cell stemness and vaccine protection @jem.org @groomlab.bsky.social @benjbroom.bsky.social
doi.org/10.1084/jem....

thanks Lucie