Seth Thomas Scanlon

Thanks, @natrevimmunol.nature.com, for highlighting this exciting recent paper in #Science #Immunology!

This week in #Science #Immunology! 👇

Decoding the Brain Tumor Immune Microenvironment. Brain tumors originate either from within the brain or as metastases from other tissues and pose major clinical challenges because of their heterogenous and aggressive nature. Bunse et al. review the cellular and molecular determinants of brain tumor antigenicity and factors that contribute to the immunosuppressive brain tumor microenvironment (TME). This month’s cover illustration depicts distinct malignant glioma (upper left) and metastatic (bottom right) TMEs as collages of aperiodic penrose tiles overlaid on a stylized positron emission tomography (PET) scan of the brain. Credit: Rioka Hayama

The October issue of #Science #Immunology is out now! This week: how #TCR avidity shapes #CD8 #TCell responses to #mRNA #vaccines and the latest research on the immunology of #brain #tumors reviewed! New content added every week!

scim.ag/46TGooP

Design of a potent interleukin-21 mimic for cancer immunotherapy A de novo IL-21 mimic, 21h10, exhibits improved stability and potent antitumor activity in vivo compared with native IL-21.

David Baker & colleagues develop an #IL21 mimic (21h10) that is more stable & shows x-reactivity against both human & murine #IL21R. 21h10 promotes potent antitumor responses in mice and in human #melanoma tumor explants, expanding low-affinity CD8 #TCells & #TH1 cells & reducing #Tregs in #tumors!

Group 2 innate lymphoid cells regulate nociceptive and gait functions of the peripheral nervous system ILC2-neuron cross-talk contributes to the maintenance of nerve structure and function of the peripheral nervous system.

Now in #Science #Immunology: Deshpande, Klose, & al at Charité—Universitätsmedizin Berlin report that #ILC2 resident in #PNS communicate with neurons via #IL13 to maintain #nerve structure & pain thresholds. Mice lacking ILC2 or whose neurons are Il4ra-KO exhibit #hypersensitivity & #gait defects!

Inhibitory immune checkpoints in cancer immunotherapy Inhibitory immune checkpoints for cancer immunotherapy are reviewed.

Out now in #Science #Immunology: Zhenghai Tang (U of Macau) & André Veillette (@ircm.bsky.social / @mcgill.ca / @umontreal.ca) review the latest research on inhibitory #ImmuneCheckpoints in #cancer #immunotherapy. Check it out!

Nuclear polarization to the immune synapse facilitates an early transcriptional burst Cytotoxic T lymphocyte target recognition triggers rapid nuclear polarization to the immune synapse and an early transcriptional burst of cytokines.

Now in #Science #Immunology: @griffithslab.bsky.social report that when #CD8 #TCells encounter their targets, #nucleus localizes to the #ImmuneSynapse (IS) & facilitates delivery of newly synthesized cytokines to the IS. They find nuclear polarization represents key step in #CTL -mediated killing!

Allergen-induced airway matrix remodeling in mice can be prevented or reversed by targeting chitinase-like proteins Allergic airway matrix remodeling occurs independently of IL-13 and IL-17A and is driven instead by chitinase-like proteins.

Now in #Science #Immunology, @drtesutherland.bsky.social & al report chitinase-like proteins (CLPs) make distinct contributions to airway pathology independent of #IL13- & #IL17 –mediated signaling in 🐀 #asthna model! CLPs orchestrate airway #ECM remodeling, & can be both protective & detrimental!

Shining a Light on Naïve T Cell Homeostasis: Homeostatic maintenance of naïve T cells is critical to maintain a large and diverse T cell pool. However, the underlying mechanisms regulating this process are not well understood. Wu et al. report that the RNA helicase DDX55 regulates the homeostatic maintenance of naïve T cells by preventing MYC from binding to enhancer- and promoter-like transposable elements (TEs) near T cell activation genes. In naïve T cells, DDX55 prevents the inappropriate activation of TEs and ensures their genomic stability by preventing R-loop formation. This month’s cover features a light bulb with its filament stylized as a DNA double helix. Its left half glows with an intact filament, symbolizing TEs as regulators, and its right side is dimmed and features a broken filament, representing TEs’ disruptive potential. Credit: Bingyu Yang and Jianling Zhu/Sichuan University

The September issue of #Science #Immunology is out! This week: METTL1 m⁷G RNA modification of NAD+ #metabolism → #macrophage -mediated #inflammation; proenkaphalin+ #Tregs restrain skin inflamm via control of #nociception; #RNA helicase DDX55 is regulator of naïve #TCell homeostasis

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Way to go, @cnfogg.bsky.social!

Heads up: @science.org is looking for a new research #editor based in the US or UK to handle papers in #InfectiousDiseases (e.g., #virology, #microbiology, #parasitology) & #microbiome research! This is an amazing opportunity, so don't delay! Applications are due 22 SEP!

Home - IUIS 2025 IUIS 2025 ACCREDITED WITH 26 CME CREDITSThe 19th International Congress of Immunology (IUIS 2025), Vienna, Austria 17/08/2025 – 22/08/2025, has been accredited by the European Accreditation Council fo...

Heads up: @science.org 's immunology editor @sarahhross.bsky.social and I will both be attending the @iuis-online.bsky.social 19th International Congress next week in the ever enchanting city of #Vienna! We hope to see many of you there!

The cover was illustrated by Rioka Hayama, who also designed #Science #Immunology 's wicked JAN 2025 cover!

riokahayama.com

COVER This illustration depicts the changes in the immune system throughout an individual’s life span, from infancy to childhood, adulthood, and older age. The infant silhouette contains DNA, and the figures are enveloped by the nuclear and plasma membranes. These components reference the evolution of immunity over millennia, as viruses integrated into the genome and as life progressed from single-celled to multicellular organisms. See the special section beginning on page 586. Illustration: Rioka Hayama

This week's @science.org #IMMUNOLOGY-themed SPECIAL ISSUE features Reviews by {Kassiotis & Stoye}, {Nahrendorf, Ginhoux, & Swirski}, {Sharma, Gibbons, & Saphire}, & {@jessmetcalf.bsky.social, @grahammunology.bsky.social, Yates, & Cummings} + an absolutely wild & wonderful cover!

scim.ag/3UqRrA6

The cover depicts an hourglass with beneficial (blue) & pathogenic (orange) microbiota drawn as sand. Transferred Tregs lining the hourglass cause the “sand” to flow in reverse, highlighting their ability to undo some of the effects of inflammaging by restoring gut barrier integrity!

CD4 T cell therapy counteracts inflammaging and senescence by preserving gut barrier integrity Treg cells safeguard the intestinal barrier to prevent inflammaging and senescence in a mouse model of premature aging.

This week's cover, illustrated by the amazing Ashley Mastin, highlights work by @mmgomezheras.bsky.social & al.!

The August issue of #Science #Immunology is out! This week: T peripheral helper cells expressing IGFL2 contribute to rheumatoid #arthritis; vagal TRPV1+ sensory #neurons protect against #influenza virus infection; & transfer of #Tregs alleviates #inflammaging in mice!

wwwscience.org/toc/sciimmun...

Innate lymphoid cells originate from fetal liver–derived tissue-resident progenitors Fetal liver–derived ILC progenitors seed peripheral tissues and generate local ILCs independently of the bone marrow throughout life.

Out now in #Science #Immunology: Eric Vivier (@univ-amu.fr), Hui Peng, Zhigang Tian (USTC, Hefei), & colleagues report that #FetalLiver #InnateLymphoidCell ( #ILC ) progenitors in mice continue contributing to ILC #hematopoiesis into adulthood in a #BoneMarrow –independent manner!

These 2 processes together fine-tune #type2 immune responses & may help explain why, for example, #IgE sensitization & development of #allergic disorders are more prevalent in males & certain groups with groups sharing genetic ancestry.

#SexDifferences in #Immunity
#HumanImmunology
#RTEexonization

Primate retroelement exonization and sexually dimorphic IL13RA1 transcription tune type 2 immune responses Co-option of primate-specific retroelements creates an alternative IL-13Rα1 subunit that tunes type 2 immune responses.

In #Science #Immunology, @tobiasplowman.bsky.social, Kassiotis, & al report canonical #IL13RA1 expression is negatively regulated by E2 #estrogen & also describe a primate-specific RTE-derived IL-13Rα1 isoform that antagonizes the canonical receptor & attenuates responsiveness to #IL4 and #IL13!

Checkpoint on Type 2 Immunity. Tuft cells play key roles in the initiation and propagation of type 2 immune responses in the gut, but whether they have regulatory machinery for constraining these responses is not known. Wang et al. found that the transcription factor Spi-B prevents excessive type 2 immune responses against helminth infection and food allergens by limiting tuft cell activation and proliferation in the small intestine. Spi-B represses c-Kit signaling in tuft cells, which limits their production of the cytokine TSLP and the subsequent activation of T helper 2 (TH2) cells. This month’s cover image features a tuft cell (dark red) within the epithelial lining of the small intestine in which Spi-B has been inactivated, leading to increased production of TSLP by tuft cells and the cytokine interleukin-13 (IL-13) by TH2 cells (white). Credit: A. Fisher/Science Immunology

The July issue of #Science #Immunology is out now! This week:

• Additional levels of #IL13RA1 gene regulation help explain susceptibility to #allergy!

• Spi-B is a #checkpoint of #type2 immunity by restraining #TuftCell activation in gut!

New content each week!

www.science.org/toc/sciimmun...

I am so delighted to be in #Japan for this year's RIKEN IMS–JSI International Symposium on #Immunology! 🇯🇵

温かく迎えてくれた主催者に感謝する！

To celebrate @focisimmunology.bsky.social 's annual meeting this week, #Science #Immunology has just released a new free sample collection of recent papers with a focus on human immunology! The collection will be available online to read until the end of July 2025! #FOCIS2025

bit.ly/SciImm_free

CLNS1A regulates genome stability and cell cycle progression to control CD4 T cell function and autoimmunity CLNS1A promotes autoimmunity through epigenetic and transcriptional regulation of DNA repair and cell cycle progression in CD4 T cells.

Out now in #Science #Immunology: using a forward genetic of #ion #channels & #transporters, @stefanfeske.bsky.social & colleagues identified chloride nucleotide-sensitive channel 1A (CLNS1A) to be a critical regulator of #CD4 #TCell proliferation & differentiation!

Inducible protein degradation reveals inflammation-dependent function of the Treg cell lineage–defining transcription factor Foxp3 Acute Foxp3 protein depletion selectively affects Treg cells responding to type 1 inflammation.

Recently in #Science #Immunology: Van der Veeken & al @ IMP @viennabiocenter.bsky.social generated 🐁 w auxin-inducible degradable #Foxp3! Tissue #Tregs minimally unaffected @ homeostasis but highly dependent on continuous Foxp3 activity in models of #autoimmunity, #viral #infection, & #cancer !

Dissection of the immune landscape in psoriatic arthritis defines immunoproteasome up-regulation in treatment resistance Refractory PsA patients exhibit dysregulated immunoproteasome and MHC-I machinery, highlighting potential therapeutic targets.

Recently in #Science #Immunology: researchers @ Weizmann & Tel Aviv Sourasky characterize synovial fluid immune compartment of #PsoriaticArthritis patients. #Immunoproteasome- & #MHCI -related genes ↑ in patients w refractory disease. Targeting immunoproteasome may be possible therapeutic approach!

PSGL-1 is a phagocytosis checkpoint that enables tumor escape from macrophage clearance PSGL-1 acts as a phagocytosis checkpoint to promote tumor immune escape through impeding LFA-1 activation in macrophages.

New in #Science #Immunology: Researchers at Sun Yat-Sen University in Guangzhou report that #BloodCancers expressing PSGL-1 can prevent the #integrin signaling #macrophages need for #phagocytosis. Targeting PSGL-1 improved survival in mouse models of #leukemia, #lymphoma, & #MultipleMyeloma!

Conventional and nonconventional functions of TFH cells: In addition to their conventional role as GC facilitators—providing survival and proliferation signals to GC B cells—TFH cells also perform noncanonical functions. They can support CD8+ T cell responses, produce effector-like cytokines that critically influence B cell fate decisions beyond GC maintenance, and exhibit TSCM properties that allow them to serve as reservoirs for pathogenic Teff cell subsets across various anatomical niches

This month in #Science #Immunology, Shivangi Dave & André Ballesteros Tato at the #NIH review the noncanonical contributions of #TFollicularHelper ( #TFH ) cells cells to immune regulation beyond their traditional roles in #BCell help!

science.org/doi/10.1126/sciimmunol.adr1052

This fantastic work by @emilyaunins.bsky.social, Anthony Phan, @drewweissmanlab.bsky.social, @kingofpathogens.bsky.social, & colleagues is featured on this month's cover of #Science #Immunology!

One of this month's excellent investigator-penned other-journal #ResearchHighlights in #Science #Immunlogy: