immunoboys

Daratumumab in lupus 🦋 – results of our single-arm trial:
10 patients 8x daratumumab (1/week) at week 12:
☑️ reduced dsDNA antibodies
☑️ Median SLEDAI 12 > 4
☑️ SRI-4 at 12 weeks 100%
☑️ immunology improved*

out now at @nature.com Communications: www.nature.com/articles/s41...
#medsky #nephsky 🧪 1/

Workflow of EBV-seq

Adapting the 10x workflow to detect EBV reads, Younis et al show that EBV-transcribing B cells are increased in SLE patients, especially among CD27+CD21low B cells. They have autoreactive BCRs and are more poised for antigen-presentation.

2025 Sci Transl Med 🧪 ⑂
www.science.org/doi/10.1126/...

CD8 T cells produce IFNg and CXCL13 in TLS

What mechanisms drive checkpoint inhibitor-associated interstitial nephritis (ICI-AIN)?
In our preprint, we identify CD8 T cells as a central player, inducing a proinflammatory myeloid cell state by IFNg and structuring lymphoid aggregates by CXCL13.

www.biorxiv.org/content/10.1...
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#Nephsky 🧪

Damgaard et al – 2016 – The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity in @cellpress.bsky.social
doi.org/10.1016/j.ce...

Ubiquitinylation is more complex than just a signal for proteasomal degradation: Linear ubiquitinylation of Methionine-1 is important for NFkB signalling.
LOF of the Deubiquitinylase OTULIN leads to an autoinflammatory disease with a TNF positive feedback loop.
🧪 ⑂
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Tregs in the skin reduce the activation of sensory neurons by producing encephalins. This inhibits secondary proinflammatory effects by neurons.

Tregs in the skin reduce the activation of sensory neurons by producing enkephalin. This inhibits secondary inflammatory changes mediated by the neurons. (in 🐭)
🧪 ⑂

Mendoza et al 2025 in Science Immunology
www.science.org/doi/full/10....

“Good things take time”

Allogeneic Treg do not prevent their own rejection in immunocompetent hosts - HLA matching or HLA editing required for optional function!

A beautiful collaboration with Fadi Issa & Joanna Hester’s team @ox.ac.uk. @dlwagnerlabs.bsky.social

Neuropeptide signalling orchestrates T cell differentiation - Nature RAMP3, a component of the receptor for the neuropeptide CGRP, has a cell-intrinsic role in T helper type 1 cell fate determination.

Hou, Sun et al from @kuchroolab.bsky.social 2024 in @natureportfolio.nature.com
"Neuropeptide signalling orchestrates T cell differentiation"

www.nature.com/articles/s41...

Figure 3 from the paper showing the experimental setup and top hits of Th1 regulators

CRISPR screening factors influencing Th1 vs Th2 differentiation, RAMP3 which forms part of a CGRP receptor is a positive regulator of Th1 differention. CGRP acts by increasing intracellular cAMP and ultimately ATF3 activity it induces STAT1 and thereby Th1 differentiation. in 🐭
🧪 ⑂ 1/2

Versatile and efficient non-viral integration of large transgenes in human T cells via CRISPR knock-in and engineered integrases Current gene transfer methods often lack the precision, versatility, or efficiency when integrating large transgenes, limiting the ability to engineer therapeutic T-cells with more complex payloads. H...

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...

From the Rao Lab and the AMP Consortium:
Horisberger et al 2025 @jclinical-invest.bsky.social
www.jci.org/articles/vie...

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
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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...
🧪⑂

Absolute neutrophil count by Duffy status among healthy Black and African American adults Key Points. The median ANC among Duffy-null individuals is significantly lower than that among Duffy non-null individuals.Nearly a quarter (23.8%) of Duffy

Duffy Null-associated neutrophil counts (DANC) does not seem to be associated with increased risk of infection.

via @curiousclinpod.bsky.social
Merz et al – 2023 @bloodjournals.hematology.org

ashpublications.org/bloodadvance...

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.

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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/...