You like engineering T cells, but you are missing the right flavor? Check out 'one-pot' PASTA recipe 🔥🍝: www.biorxiv.org/content/10.1101/2025.09.10.675267v1 We combined a unique mix of CRISPR knock-in with serine integrases for easy-to-adopt 𝐏rogrammable 𝐀nd 𝐒ite-specific 𝐓ransgene 𝐀ddition 🧪

Plasmacytoid dendritic cells can transition to become cDC2s under to influence of TNF, while type-I interferon reduces TNFR expression and thereby inhibits transition. These transitioned cDC2 seem fully functional. 🧪 ⑂ Hornero et al 2025 in Nat Immunol www.nature.com/articles/s41...

Horisberger et al separate Lupus nephritis patients in 3 groups by blood: healthy-like, interferon-dominant and CD8 T cell-dominant. The CD8 T cell-dominant group had the highest biopsy activity score and highest response rate after 1 year; the healthy-like the most chronic damage. 🧪 ⑂ #NephSky 1/

A synonymous mitochondrial variant is negatively selected against in short-lived CD8 effectors – How? The variant changes tRNA pairing from Watson-Crick-Franklin to wobble, thereby reducing translational efficiency in high energy demand. 🧪 ⑂ Lareau et al – 2025 www.pnas.org/doi/10.1073/...

Effector CD8 T cells have punctate mitochondria with loose cristae, favoring glycolysis and memory T cells elongated mitochondria with tight cristae, favoring OxPhos. Pharmacologic remodeling of mitochondria improves Teffs in adoptive transfer. 🧪 ⑂ Buck et al 2016 doi.org/10.1016/j.ce...

In Lupus nephritis patients, neutrophils have increased surface LAMP1, which is externalized after activation. Soluble LAMP1 is increased both in the blood and urine of patients, correlating with histological activity. #NephSky 🧪 Our paper in @eurjimmunol.bsky.social doi.org/10.1002/eji....

Resting MAIT cells generally express the non-cytotoxic Granzyme K, but rapidly switch to the cytotoxic Granzyme B upon stimulation. Consequently, previously stimulated MAITs kill much more target cells than resting ones. 🧪 Kurioka et al – 2015 – @mucosalimmunol.bsky.social doi.org/10.1038/mi.2...

MR1-presented cholic acid 7-sulfate + 3-sulfate are endogenous stimulatory ligands for MAIT cells. Stimulation is much weaker than by traditional ligand 5-OP-RU, potentially contributing to steady state activation and thymic generation of MAITs. Ito et al 2024 www.science.org/doi/10.1126/...

Oxidized mitochondrial DNA induces NLRP3 activation in pDCs. This leads to enhanced pDC function beyond IFNa production so that they produce IL1b, IL6 and IL21, inducing Tfh differentiation and autoimmunity (in 🐭). Xian et al – 2025 @natureportfolio.nature.com www.nature.com/articles/s41... 🧪⑂

Individuals of subsaharan ancestry often have a Duffy Null blood group. DARC (the Duffy protein) is a multi-chemokine sink on red blood cells. Duffy Null people have lower peripheral blood neutrophil counts, likely resulting from increased neutrophil egress into the periphery. 1/2

I thought my scRNA data is bad with all the plasmacytoid dendritic cells expressing Granzyme B. Turns out, human pDCs are known producers of Granzyme B and deliver it to T cells, inhibiting T cell expansion. 🧪⑂ Jahrsdörfer et al 2010 in @bloodjournals.hematology.org doi.org/10.1182/bloo...

S1P is produced in the outer lymph follicle area and degraded by B cells resulting in a negative gradient towards to follicle center. S1PR2 signalling on GC B cells leads to migration arrest, keeping B cells within the follicle. (🐭 data) Green et al 2011 🧪⑂ www.nature.com/articles/ni....

Succinate induces Treg dysfunction by inhibiting succinyl-CoA generation. Succinyl-CoA is necessary for FOXP3 succinylation and protection of FOXP3 from proteasome degradation. Wang et al – 2025 @natureportfolio.nature.com www.nature.com/articles/s41...

We would like to acknowledge the consistent support of the baristas at #FOCIS2025 in Boston. Keeping us fueled through all the great science over the last few days. @focisimmunology.bsky.social 🧬🧪☕️

Human naive CD4 T cells cultured in high sodium and Th17 polarising conditions will produce much more IL-17 than in normal sodium conditions, an effect mediated by p38/MAPK and SGK1. Kleinewietfeld et al 2013 @natureportfolio.nature.com www.nature.com/articles/nat... #throwbayfriday 🧪⑂

Both @immunoboys.bsky.social will be at FOCIS next week - looking forward to cool science in beautiful Boston. 🧪🔬

Join us June 24-27, 2025, in the vibrant city of Boston, MA! If you haven't already, we recommend registering early. Rates go up the longer you wait! You can find all the details, including registration information, on the FOCIS 2025 website: zurl.co/vV0m6

Mice with low fecal IgA might be colonized be the auxotrophic Tomasiella immunophile which degrades kappa LC immunoglobulins in gut and induces disease-relevant reductions in intestinal IGs. 🧪⑂ Lu et al 2024 @science.org www.science.org/doi/10.1126/...

A 🐭 without Furin in T cells develops a spontaneous autoimmune disease with colitis and autoantibodies. This is likely because Furin in Tregs is necessary to activate TGFb, but also Furin-/- Tcons are less suppressable. #throwbayfriday 🧪⑂ Pesu et al 2008 www.nature.com/articles/nat...

After degranulation, mast cells attract neutrophils with LTB4 and trap them inside. These trapped neutrophils provide the mast cells with nutrients and lend them neutrophil abilities like expulsing NETs and proteases. Mihlan et al 2024 @cellpress.bsky.social www.cell.com/cell/fulltex...

Analysing paired samples of human blood and thoracic duct lymph, Buggert &al show that human CCR7- non-resident memory CD8 T cells separate into a CX3CR1+ exclusively intravascular, cytotoxic and a non-cytotoxic, lymphatic population. 2020 in @cellpress.bsky.social 🧪⑂ www.cell.com/cell/fulltex...

Exhausted CD8 T cells express the Beta-1 adrenergic receptor (ADRB1) and are found near sympathetic nerves. Activation with catecholamines leads to reduced TCR signalling and T cell function, while beta-blockade helps 🐭 Globig et al 2023 @natureportfolio.nature.com 🧪⑂ www.nature.com/articles/s41...

We think of Tregs having no PI3K/Akt/mTOR activation or glycolytic switch after CD3/CD28 stimulation. However, TNFR2 costimulation actually induces glycolytic flux via mTORC1, contributing to their suppressive function and stability. www.nature.com/articles/s42... De Kivit et al 2020 🧪⑂

🚨 A bold approach to treating severe autoimmunity: We explored CRISPR-Cas9 mediated deletion of the PR3 autoantigen in blood stem cells as a strategy for ANCA-associated vasculitis. 🧬 Great idea and execution by Kettritz lab @bihatcharite.bsky.social #ChariteBerlin 🔗 doi.org/10.1016/j.ki... 🧪

Fenestrated endothelium enables the extravasation of immune complexes into the synovium. There the interaction of macrophages (producing IL1b, CXCL1) and nociceptive neurons (producing CGRP) induce pain and inflammation. Hasegawa &al 2024 www.nature.com/articles/s41... #RheumSky 🧪⑂

First fruit of my postdoc in the Rao lab: Our "Nephrology Digest" article on the roles of ILCs, GM-CSF and disease-associated macrophages in lupus nephritis @kidneyint.bsky.social authors.elsevier.com/a/1k-ypJOcpz... #NephSky #ImmunoSky 🧪

Jobin et al discover a second priming phase of CD8/DC interaction in the subfollicular LN area. CXCR3+ high-affinity CD8s can get IL-2 from "stop-and-go" moving CD4+ TCs, inducing affinity selection while Tregs mop up IL-2. in 🐭 @science.org 🧪⑂ 1/2 www.science.org/doi/10.1126/...

Tissue-resident memory T cells have high levels of mRNA of proinflammatory cytokines but produce the proteins only upon stimulation. 🧪⑂ The integrated stress response inhibits mRNA translation in these cells, having these cells poised for rapid responses in 🐭 and 🧓. 1/2

PD1 expression in Tfh cells leads to reduced PI3K activation, counteracting CXCR5. In this situation, ICOS signalling is needed to overcome this stalemate to induce GC migration. Plus PD1 is needed for optimal IL-21 production and stringent GC selection. in 🐭 Shi &al 2018 🧪⑂ doi.org/10.1016/j.im...

CD62L marks a progenitor subset of the progenitor-exhausted CD8 T-cell in mice with chronic LCMV infection and the transcription factor MYB is important for this state. Conditional MYB -/- leads to hyperinflammation, illustrating exhaustion as an adaptive state. doi.org/10.1038/s415... 🧪

GGG is a ligand to the migration inhibitory receptor P2RY8. GGG is inactivated by GGT5 which is highly expressed by follicular DCs. Together this forms a "negative chemokine gradient", where germinal center BCs are confined to the GC. Lu et al 2019 www.nature.com/articles/s41...

Tracking antigen-specific CD8 T cells in the 🐭 intestine during LCMV infection over time: Trm precursors are found more in the base of villi, while mature Trm cells are found at the top of the villi, driven by TFGb. @reinacampos.bsky.social &al 2025 in Nature www.nature.com/articles/s41...

During inflammation, CCL21 is down-regulated in the lymph node. Enzymes for production of oxysterols are induced and recruitment of naive/central memory cells relies more in oxysterols interacting with GPR183 (+ CCL19). in 🐭 Chen et al @cellpress.bsky.social 2025 pubmed.ncbi.nlm.nih.gov/39708807/

Lactat transporter MCT11 seems to enable exhausted CD8+ T cells to go deeper into hypoxic tumors but also contributes to exhaustion. Blockade or KO leads to improved anti-tumor responses, especially in high lactate tumors. (in 🐭) Peralta et al – 2024 www.nature.com/articles/s41...

What controls homeostatic vs inflammatory Th17? TCF1 is higher in in homeostatic Th17 cells and directly binds RORγt. IL-23 reduces TCF1 (in a very nice dose-dependency) and a Tcf7-/- is sufficient to induce inflammatory Th17. Magnani et al 2024 et @cp-immunity.bsky.social doi.org/10.1016/j.im...

Matured plasmacytoid DCs increase ICOS-L expression while myeloid DCs reduce ICOS-L expression after stimulation – pDC-derived stimulation of induces IL-10 producing, suppressive T cells. Ito et al – 2007 @jem.org rupress.org/jem/article-...

T cells acquire both TCRs and CARs from other activated T cells by trogocytosis. Notably, this trogocytosis does not need a cognate receptor/ligand. Modifying CAR transmembrane domains makes trogocytosis more/less likely. @barbera-stefano.bsky.social et al 2025 www.science.org/doi/10.1126/...

Gender-affirming testosterone treatment in trans men leads to an immune system bias towards TNF and away from a type I interferon response, evidenced by decreased pDCs, more TNF/less IFN I after stimulation of monocytes – Dysentangling genetic vs endocrine effects of immune system differences. 1/2

Human PD1 has both higher affinity to PD-L1 and better recruitment of its SHP2 effector phosphatase compared to 🐭. The coolest thing is however the functional assay of reconstructed PD1 ic domains over the phylogenetic tree: Masubuchi et al Sci Immunol 2025 www.science.org/doi/10.1126/...

Preprint from the Rao lab: CD57+ Tem CD8 cells are associated with interstitial lung disease in Systemic Sclerosis. One mechanism seems to be co-stimulatory CD226 interacting with CD155 on damaged epithelial cells. Sasaki et al 2025 on www.biorxiv.org/content/10.1...

PD1 engagement on activated T cells induces fatty acid oxidation (and inhibits glycolysis), setting them on a metabolic path towards memory T cell generation. Patsoukis et al 2015 in Nat Commun: www.nature.com/articles/nco...

IFN-stimulated inflammatory monocytes can cross-dress in cancer cell-derived MHC-I complexes to stimulate CD8 T cells (in 🐭 melanoma). Prostaglandin E2 inhibits this function in monocytes, so combining IFN-I stimulation + COX inhibition improves cancer immunity. 1/2 www.nature.com/articles/s41...

Influenza infection induces CXCL13 production in pulmonary fibroblasts (via type I IFN). The CXCR5/CXCL13 axis recruits naive B cells to lung, building TLS with germinal centre action and plasma cell generation happens. (in 🐭) Denton &al 2019 from @linterman.bsky.social lab doi.org/10.1084/jem....

In a lupus nephritis model, not just the kidney medulla is hypoxic (as normal), but also the cortex. It seems that metabolic adaptations to hypoxia in T cells is associated with inflammation. Blocking HIF1a improved nephritis (🐭), likely by depleting plasma cells, but also removing T cells 1/2

IFNg stimulation induces SLAMF7 expression on myeloid cells in rheumatoid arthritis. SLAMF7 engagement (with recombinant SLAMF7) then leads to a strong increase in a large number of proinflammatory mediators. SLAMF7+ are found in a number of inflammatory conditions. 1/

UV-irradiation of the skin leads to an accumulation of photo-labeled neutrophils in the kidney, accompanied by increase in kidney damage transcripts and subclinical albuminuria. Skopelja-Garner et al 2021 in PNAS www.pnas.org/doi/10.1073/...

The Th17 cytokine IL-26 (which 🐭 don't have) moonlights as an antimicrobial peptide, lysing bacteria and packaging free DNA for pDC stimulation. Meller et al 2015 in Nature Immunology www.nature.com/articles/ni....

USP30 -/- leads to overshooting mitophagy – 60% of CD8 T cells did not have any mitochondria at day 5 of stimulation and showed decreased cytotoxicity. The mechanism is however not ATP depletion but reliance on mitochondrial protein synthesis to produce new granzyme/perforin after stim 🤯 1/