Immunity

Inflammation in atherosclerosis: Lessons and therapeutic implications Cardiovascular risk factors can spark inflammation by eliciting misdirected responses of intrinsic vascular cells and leukocytes, culminating in lesion initiation, progression, and complication. Soehnlein and Libby review key underlying inflammatory mechanisms in atherosclerosis and discuss how new understanding based on increasingly sophisticated tools has enabled translation to the clinic.

Online now: Inflammation in atherosclerosis: Lessons and therapeutic implications

Obesity, diabetes, and inflammation: Pathophysiology and clinical implications Obesity and its related disorders are now recognized as chronic inflammatory conditions. Donath and Drucker review the mechanisms underlying inflammation in these settings and discuss how understanding the mechanisms whereby Glucagon-like peptide-1 (GLP-1) receptor agonists function may unlock further therapeutic potential in chronic inflammatory diseases.

Online now: Obesity, diabetes, and inflammation: Pathophysiology and clinical implications

Eomes controls the acquisition of regulatory and cytotoxic function in CD4+ T cells that are critical for limiting immune toxicity, while maintaining persistence and tumor control after immunotherapy @cp-immunity.bsky.social
www.cell.com/immunity/ful... @fredhutch.org

The transcriptional repressor BLIMP1 enforces TCF-1-dependent and -independent restriction of the memory fate of CD8+ T cells TCF-1, encoded by Tcf7, supports CD8+ T cell memory and is silenced in effector T cells. Murphy et al. identify two cis-elements required for Blimp1-mediated Tcf7 repression and find that decoupling Tcf7 silencing from effector differentiation is permissive for effector gene expression. Thus, Blimp1 restricts memory differentiation through both Tcf7-dependent and -independent pathways.

Online now: The transcriptional repressor BLIMP1 enforces TCF-1-dependent and -independent restriction of the memory fate of CD8+ T cells

Oxidative-stress-induced telomere instability drives T cell dysfunction in cancer The tumor microenvironment (TME) imposes immunologic and metabolic stresses sufficient to deviate immune cell differentiation into dysfunctional state…

The paper, led by Dayana Rivadeneira and @delgoffelab.bsky.social, is now published in @cp-immunity.bsky.social buff.ly/EmyQx1w (2/2)

Notch3 destabilizes regulatory T cells to drive autoimmune neuroinflammation in multiple sclerosis Benamar et al. demonstrate that Notch3+ Treg cells are increased in multiple sclerosis and in EAE. They are induced in the gut by microbiota and translocate to the CNS to degenerate into pathogenic Th17 cells. They also outcompete a protective NPY1R+-resident Treg cell population that controls Th1 responses.

Online now: Notch3 destabilizes regulatory T cells to drive autoimmune neuroinflammation in multiple sclerosis

Eomesodermin+ CD4+ T cells are critical for curative immunotherapy outcomes Type-1 regulatory T cells (Tr1) promote immune tolerance during chronic infection, autoimmunity, and transplantation, but the role of Eomes in Tr1 differentiation and function after cell therapy is unclear. Zhang et al. find that Eomes controls the acquisition of regulatory and cytotoxic function in CD4+ T cells that are critical for limiting immune toxicity, while maintaining persistence and tumor control after immunotherapy.

Online now: Eomesodermin+ CD4+ T cells are critical for curative immunotherapy outcomes

Congrats to Dr. Sing Sing Way @babiesresearch.bsky.social and team at the Center for Inflammation and Tolerance @cincychildrens.bsky.social for shedding fresh light on how #microchimerism works. Read more on our science blog: scienceblog.cincinnatichildrens.org/deeper-micro...

S. aureus causes a basophil influx into skin-draining lymph nodes that heightens Th2 responses & increases serum IL-4, which enhances intestinal permeability, exaggerating oral anaphylaxis (dermatitis --> food allergy) @cp-immunity.bsky.social @harvardmed.bsky.social
www.cell.com/immunity/ful...

Sharing the latest from the @babiesresearch.bsky.social lab!

Microchimeric cells transfer bidirectionally during pregnancy. These uninherited cells are rare, but also heterogeneous. My coauthors devised a way to target lineage specific cells and their role in promoting tolerance.

Intra-tumoral hypoxia promotes CD8+ T cell dysfunction via chronic activation of integrated stress response transcription factor ATF4 Metabolic stress imposed by the tumor microenvironment (TME) promotes T cell dysfunction and limits antitumor immunity. Alicea Pauneto et al. demonstrate the hypoxia within the TME drives chronic activation of ATF4, which promotes metabolic polarity and cell death of tumor-infiltrating CD8+ T cells (TILs). ATF4 integrates tumor hypoxia and mitochondrial defects in TILs.

Online now: Intra-tumoral hypoxia promotes CD8+ T cell dysfunction via chronic activation of integrated stress response transcription factor ATF4

Control of myeloid lineage fidelity and response to stimuli by ISWI-enforced nucleosome phasing Polletti et al. show that in macrophages, ISWI chromatin remodelers preserve nucleosome arrays flanking PU.1-bound sites. ISWI deficiency enabled binding of the transcriptional regulator C/EBPβ to non-myeloid genomic regulatory elements, driving lineage-inappropriate transcription and exaggerated and stimulus-mismatched gene activation. Their findings point to nucleosome phasing as an important regulator of lineage fidelity and immune cell activation.

Online now: Control of myeloid lineage fidelity and response to stimuli by ISWI-enforced nucleosome phasing

S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis S. aureus skin colonization is associated with food allergy in atopic dermatitis, but the mechanism of this association is unknown. Das et al. reveal that cutaneous exposure to S. aureus causes a basophil influx into skin-draining lymph nodes that drives a heightened T helper-2 response to simultaneously encountered antigen with increased serum IL-4 concentration, which enhances intestinal permeability, exaggerating oral anaphylaxis.

Online now: S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis

Excited for this article! Defining B cells has always felt messy and hard to follow. Hoping this brings some clarity.

Rod-shaped microglia interact with neuronal dendrites to attenuate cortical excitability during TDP-43-related neurodegeneration @cp-immunity.bsky.social @uthealthhouston.bsky.social @mayoclinic.org
www.cell.com/immunity/ful...

Perspective @cp-immunity.bsky.social A roadmap for defining “extrafollicular” B cell responses
www.cell.com/immunity/ful... @stephanieeisen.bsky.social @vinuesalab.bsky.social et al

A roadmap for defining “extrafollicular” B cell responses The term “extrafollicular” is now being used expansively to describe a variety of B cell processes beyond the original use of the term, potentially obscuring important distinct immunological processes. We discuss current uses of the term extrafollicular and propose a framework to help classify these evolving concepts in B cell biology.

Online now: A roadmap for defining “extrafollicular” B cell responses

Rod-shaped microglia interact with neuronal dendrites to attenuate cortical excitability during TDP-43-related neurodegeneration While microglial activation is a hallmark in neurodegeneration, the specific role of microglia in disease-related cortical excitability remains unknown. Xie et al. reveal that rod-shaped microglia form in response to early cortical hyperactivity in a mouse model of TDP-43 neurodegeneration. These specialized microglia interact with neuronal dendrites and remodel excitatory inputs, providing a neuroprotective effect.

Online now: Rod-shaped microglia interact with neuronal dendrites to attenuate cortical excitability during TDP-43-related neurodegeneration

A TLR4-dependent fibroblast-monocyte axis in tumor-draining lymph nodes contributes to metastasis in triple-negative breast cancer Triple-negative breast cancer (TNBC) is characterized by high risks of relapse or metastatic disease. Mattavelli et al. identify a chemokine axis that recruits immunosuppressive monocytes to tumor-draining lymph nodes. By co-targeting this recruitment, the TNBC response to immune checkpoint blockade is augmented and metastasis to the lung is reduced.

Online now: A TLR4-dependent fibroblast-monocyte axis in tumor-draining lymph nodes contributes to metastasis in triple-negative breast cancer

A TLR4-dependent fibroblast-monocyte axis in tumor-draining lymph nodes contributes to metastasis in triple-negative breast cancer @cp-immunity.bsky.social
www.cell.com/immunity/ful...

CD103 facilitates the interaction of naive CD8+ T cells with E-cadherin-expressing dendritic cells that in turn provide cytokine-mediated cues to promote their differentiation into memory-phenotype effector T cells @cp-immunity.bsky.social
www.cell.com/immunity/ful...

Integrin CD103 expression in naive CD8+ T cells promotes cytokine-driven acquisition of memory phenotype and effector function Integrin CD103 mediates memory T cell tissue residency by binding E-cadherin-expressing epithelial cells, but why CD103 is also expressed on circulating naive CD8+ T cells has been unclear. Li et al. ...

#InterferonPower! Li, Park &co show @cp-immunity.bsky.social that IL-15 negatively regulates CD103 expression on CD8 T cells allowing formation of effector T cells & that engagement of CD103 on CD8 T cells by E-cadherin+ dendritic cells is necessary to drive memory formation via type I IFNs & IL-12

Integrin CD103 expression in naive CD8+ T cells promotes cytokine-driven acquisition of memory phenotype and effector function Integrin CD103 mediates memory T cell tissue residency by binding E-cadherin-expressing epithelial cells, but why CD103 is also expressed on circulating naive CD8+ T cells has been unclear. Li et al. report that CD103 facilitates the interaction of naive CD8+ T cells with E-cadherin-expressing dendritic cells that in turn provide cytokine-mediated cues to promote their differentiation into memory-phenotype effector T cells.

Online now: Integrin CD103 expression in naive CD8+ T cells promotes cytokine-driven acquisition of memory phenotype and effector function

Multi-scaled transcriptomics of chronically inflamed nasal epithelium reveals immune-epithelial dynamics and tissue remodeling in nasal polyp formation Chronic rhinosinusitis (CRS) is driven by poorly understood immune-epithelial crosstalk. Liao et al. present a single-cell and spatial transcriptomic atlas of CRS, revealing how immune and epithelial cells interact to drive tissue remodeling and inflammation. This resource provides insight into disease mechanisms and offers a valuable framework for studying chronic inflammatory disorders of the airway.

Online now: Multi-scaled transcriptomics of chronically inflamed nasal epithelium reveals immune-epithelial dynamics and tissue remodeling in nasal polyp formation