Eva-Lena Stange

Peripheral immune-inducer dendritic cells drive early-life allergic inflammation - Nature Early-life exposure to allergens triggers a distinct local mode of dendritic cell activation in neonatal skin without requiring migration to lymph nodes, which shapes responses to allergens in later l...

New exciting #NeonatalImmunology paper: Peripheral immune-inducer dendritic cells drive early-life allergic inflammation (1/5) www.nature.com/articles/s41...

Seeon - Deutsche Gesellschaft für Hygiene und Mikrobiologie Microbiota, Probiotics and Host    Seeon- Save the date 2026 Registration Abstract Template 2026   We are looking forward to meeting you there! Don’t forget your swimwear, sunscreen and running gear ...

Registration for the 18th Annual Seeon Conference on Microbiota, Probiotics and Host is now open! 🎉

We’re looking forward to welcoming you in Seeon!

When: June 24-26
Where: Seeon Monastery, Germany (near Munich)
Program: www.dghm.org/seeon/
Registration: app1.edoobox.com/SPP1656/Seeo...

Thanks Michael!

🎉 thread with short highlight recap here: bsky.app/profile/eva-...

Taken together: The neonatal liver undergoes a developmentally hard-wired Treg wave facilitated by cDC1s needed to restrain activation and promote tolerance in conventional T cells that respond to both microbes and self in early life. (10/10)
Link: tinyurl.com/neoliver

Graphic illustrating the experimental design of the HFD experiment. Neonatal mice were Treg depleted at PND2,4,6 and then lived on a normal chow diet until 10 Weeks after birth - then, they were set on a high fat diet for 4 months. In male mice, neonatal Treg depletion leads to increased weight gain, and a proinflammtory T cell priming in the HFD (more IFNg+ and IL17+ cells as well as more Helios+ Tregs)

Yet, early-life Treg depletion also comes at a cost for long-term liver homeostasis: male mice depleted neonatally showed increased weight gain and steatosis, plus an aberrant T cell response when challenged with a high-fat diet --> even 2 months after the neonatal depletion window. (9/10)

Kaplan Meier Survival curves showing the % of mice with viremia in the blood at different time points after infections. In adults, all mice have cleared 21 days after infections, while neonatally infected mice only clear after 42 days. When Tregs are depleted during infection in neonatal mice, clearance is faster (dpi 35 instead of 42)

So what does this Treg-rich microenvironment do? We teamed up with the Billerbeck lab using the NrHV model (HCV-like hepacivirus). Neonates showed delayed viral clearance. Treg depletion accelerated clearance - strong evidence that this regulatory setpoint shapes antiviral control. (8/10)

Spatial transcriptomics picture showing a piece of neonatal liver tissue with T cell/DC clusters and expression of several marker genes. On the right side, there are bargraphs showing decreased Treg frequencies in CD11cCre MHCII flfl mice and Batf3 KO mice that do not have MHCII expression on DCs or DC1 respectively.

To understand where this happens, I designed a liver-immune–centric Xenium panel. Spatial mapping revealed that cDC1 colocalize with T cells in microclusters and are required for Treg accumulation. We also saw high Cxcl10 expression within clusters (ideas on the driver/source welcome 👀). (7/10)

This points to Tregs acting as a developmentally encoded control mechanism in early life. Notably, T cell activation in neonatal liver reaches adult-like levels by ~P7, whereas gut T cell activation is delayed until weaning. (6/10)

heatmaps showing the fold change of Treg frequency and of % of act Tconv across different microbial exposure models

We sanity-checked across multiple microbial exposure models - antibiotics, OMVs, reversible colonization (thanks to @ganalvonarburg.bsky.social+@societymucosalimm.bsky.social for technique sharing grant!) and wildlings@srosshart.bsky.social. No changes in Tregs, but increased Tconv activation (5/10)

bar graphs showing no difference betweenn spf and gf pups at pnd7 in Treg frequency in liver, spleen or cLN, and decreased Tconv activation (CD44hi expression) in GF pups in liver tissue, but not in cLN or spleen

As neonatal Treg waves in lung/gut/skin have been proposed to be microbiota-dependent, we asked whether liver Tregs would drop in germ-free mice. Surprise: they did not. In contrast, liver Tconvs specifically responded to microbial stimuli: they were less activated in germ-free pups. (4/10)

UMAPs showing distribution of T cells at PND4, 7 and in adult livers and R20 value showing a pronounced minimum at PND7 and 10 indicating clonal T cell expansion at these days

We deeply profiled liver Tregs across time (scRNA-seq + flow cytometry) and found pronounced clonal expansion and activation shift in early postnatal days: from a naïve-like state to a highly suppressive effector program at the peak of the neonatal liver T cell wave. (3/10)

Graphic displaying the kinetics of Tregs and Tconvs in the neonatal liver (a wave peaking at PND7 and PND9 respectively) and immunfluorescence pictures of clusters of T cells in the neonatal liver

Like others, we observed a wave of Tregs in neonatal WT liver during week 1–2 after birth. But it wasn’t just Tregs: CD4⁺ Tconvs and CD8⁺ T cells were also highly enriched vs adult liver, and in situ we saw T cell microclusters containing Tregs in hepatic tissue. (2/10)

Neonatal liver niches program T cell tolerance After birth, the immune system must learn to tolerate a rapidly changing milieu of commensals and self while remaining ready for pathogens. Here we characterize the neonatal liver as a central hub in ...

www.biorxiv.org/content/10.6...

Excited to share the preprint of my PhD work with @ntorow.bsky.social! We asked what T cells in the neonatal liver are doing. Main takeaways: they’re activated before weaning (unlike in most organs), show distinct microbial sensitivity, form microclusters, and have long-term consequences. 🧵⏬(1/10)

Fraudulent Scientific Papers Are Rapidly Increasing, Study Finds

'The best explanation Dr. Amaral sees for the pattern of this network is that paper mills are creating banks of images that they use to create entire batches of papers, which they then peddle to certain corrupt editors. After a while, the paper mills make new images and find new targets.'

I am co-organizing this fantastic meeting on #earlylifeimmunity in beautiful Freiburg 😍. Abstract submission until Dec 15th!
#CRC359 #DFG

www.perinatal-immunity.de/en/symposium...