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Simon Grassmann 草人

@simongrassmann.bsky.social
1.7K followers 282 following 23 posts

Immunologist in lab of Joe Sun (太阳酒) K99 @NIAID for studying STAT signaling in immune cells Occasionally I write about science and politics for Jacobin 🔬🌈🌹

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Simon Grassmann 草人 @simongrassmann.bsky.social · 30/01/2026
Mechanistically, strong antigen stimulation leads to increased AP-1 factor activity and STAT4 relocation, just like in NK cells. Together, our data suggests that IL-12/STAT4 has a context dependent role for cytotoxic lymphocytes: and the timing and strength of preceding antigen is key!
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Simon Grassmann 草人 @simongrassmann.bsky.social · 30/01/2026
However, we found that for T cells the mechanism was conserved in a different way: IL-12 signaling depended on antigen strength. In T cells with a strong TCR (from our paper Straub et al. 2023), IL-12 signaling boosted CD8+ T cell memory. But in "weak" T cells the opposite was the case.
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Simon Grassmann 草人 @simongrassmann.bsky.social · 30/01/2026
Together, this suggested to us that timing matters a lot for adaptive NK cell responses: If an NK cell receives early antigen signaling, IL-12 boosts an adaptive fate. But without this early antigen signal, the NK cells are driven into a terminal effector fate, and cannot proliferate.
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Simon Grassmann 草人 @simongrassmann.bsky.social · 30/01/2026
We used to think that NK cells in general love to receive IL-12 signaling and that IL-12 boosts proliferation via STAT4 in all NK cells. But we found that IL-12 in fact shuts down proliferation - unless the NK cell received antigen signaling first.
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Simon Grassmann 草人 @simongrassmann.bsky.social · 30/01/2026
Mechanistically, this was dependent on AP-1 factors, which are activated after antigen signaling and lead to chromatin opening. Inhibiting AP-1 prevented the opening of chromatin and subsequent relocalization of STAT4. Next, we wanted to know if this has any effect on the NK cell fate..
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Simon Grassmann 草人 @simongrassmann.bsky.social · 30/01/2026
...After antigen signaling changed chromatin accessibility, induced STAT transcription factors were relocated. But this was not the same for all: IL-12 dependent STAT4 showed the clearest change in genomic binding. This meant that NK cells receiving this early antigen signal sensed IL-12 different.
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Simon Grassmann 草人 @simongrassmann.bsky.social · 30/01/2026
These early antigen primed NK cells mounted far better adaptive responses than NK cells which had not received early antigen signaling. We thought that this may affect how cytokine signals are integrated later. Indeed, we found that antigen signaling changes how the genome is "packaged"...
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Simon Grassmann 草人 @simongrassmann.bsky.social · 30/01/2026
We used to think during MCMV infection that NK cells are first recruited to infection sites via cytokines and then can recognize antigen. My previous paper put that into question (Flommersfeld et al. 2021), and indeed we found that a portion of NK cells actually FIRST sees antigen and then cytokines
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Simon Grassmann 草人 @simongrassmann.bsky.social · 07/03/2025
Traveled to DC today for the Stand Up for Science rally ❤️🔬 We need public funding of science, no cuts!
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