Renowned for driving interferon responses, the cGAS-STING pathway reveals a surprising role: lysosomal biogenesis. In this issue of Immunity, Xu et al. uncover how STING activates the transcription factor TFEB, linking innate immune sensing to enhanced pathogen clearance through lysosomal activity.

Can bacteria that breach mucosal barriers drive long-lasting changes in immunity? In this issue of Immunity, Robles-Vera et al. describe how, in the context of colitis, bacteria breaching the intestinal barrier reprogram precursors in the bone marrow via Mincle-dependent signaling.

Indirect CD4+ T cell allorecognition of donor peptides presented by host MHC class II antigens contributes to transplant rejection in part by eliciting donor-specific antibodies (DSAs). In this issue of Immunity, Zhanzak et al. revisit the role of indirectly alloreactive CD4+ T cells in transplantation and demonstrate that immunodominant epitopes stimulate a narrow repertoire of T cells that can be

The enteric nervous system is a key regulator of inflammation, crosstalking directly with the immune system at the mucosal surfaces of the gastrointestinal tract. In this issue of Immunity, Wang and colleagues demonstrate that intrinsic enteric neurons (iENs) sense interleukin (IL)-13 to restrain group 2 innate lymphoid cell (ILC2) activity during helminth infection, uncovering a novel neuro-immune-regulatory

In a recent work reported in Science, Zhang et al. untangle dynamic changes arising across aging in multiple cell populations within thirteen organs using single-cell transcriptomics and identify four distinct dynamic waves in which immune cells are the most affected populations.

As a highly diverse and mobile organ, the immune system is uniquely equipped to participate in tissue responses in a tunable manner, depending on the number, type, and nature of cells deployed to the respective organ. Most acute organismal stressors that threaten survival—predation, infection, poisoning, and others—induce pronounced redistribution of immune cells across tissue compartments. Here, we

(Immunity 57, 2380–2398.e1–e6; October 8, 2024)

Mitochondria play critical roles in intrinsic apoptosis and NLRP3 inflammasome activation, but how these processes are interconnected remains unclear. In this issue of Immunity, Saller et al. unveiled the complexity of NLRP3 activators, highlighting mitochondria’s roles in switching apoptosis to NLRP3 inflammasome activation.

The mechanisms underpinning susceptibility to influenza virus infection, resulting in life-threatening disease, are not well understood. In this issue of Immunity, Chakraborty et al. demonstrate that sialylated IgG suppresses NF-κB-driven inflammatory responses in the lungs by inducing repressor element-1 silencing transcription factor (REST) to prevent excessive inflammation without impacting viral

Immune activation during sustained stress typically worsens stress-related psychopathology. Whether it can enhance stress resilience remains unclear. In this issue of Immunity, Xia, Lu, Lan et al.1 uncover an anxiolytic function of intestinal IL-22 pathway, which protects against psychological stress.

Inhibiting T cell exhaustion is an attractive cancer immunotherapy strategy. In this issue of Immunity, Waibl Polania et al. examine the microenvironmental signals regulating terminal T cell exhaustion and find that antigen presentation by tumor-associated macrophages, not tumor cells, drives terminal T cell exhaustion in glioblastoma.

Interleukin-17 plays a major role in controlling adipose tissue homeostasis. In a recent study published in Nature, Douglas et al. demonstrate that time-of-day-dependent expression of interleukin-17 by tissue-resident innate lymphocytes in the adipose tissue drives circadian regulation of adipose tissue homeostasis and function.

Ischemic stroke and vascular cognitive impairment, caused by a sudden arterial occlusion or more subtle but protracted vascular insufficiency, respectively, are leading causes of morbidity and mortality worldwide with limited therapeutic options. Innate and adaptive immunity have long been implicated in neurovascular injury, but recent advances in methodology and new experimental approaches have shed

There is a renewed interest in neutrophil biology, largely instigated by their prominence in cancer. From an immunologist’s perspective, a conceptual breakthrough is the realization that prototypical inflammatory, cytotoxic leukocytes can be tamed to promote the survival and growth of other cells. This has sparked interest in defining the biological principles and molecular mechanisms driving the adaptation

There are many dimensions to scientific life. We asked investigators about the impact of service to the scientific community and beyond and how service has shaped their experience, perspective, and research path.

Despite protective roles in various type of infection and in would healing, T helper (Th)2 cells are drivers of inflammation in allergic asthma. In this issue of Immunity, Zou et al. demonstrate the crucial involvement of hypoxia inducible factor (HIF)2α in promoting the differentiation of inflammatory Th2 cells, suggesting HIF2α as a promising therapeutic target for the treatment of allergic asthma

Hidradenitis suppurativa (HS) is a severe chronic inflammatory skin disease with limited response to therapy. In this issue of Immunity, Yu et al.1 identify skin tertiary lymphoid structures (TLSs) as primary sites for lymphocyte clonal expansion and autoantibody production, driving disease progression, and provide insight into how formation and maintenance of TLS impact therapeutic outcomes.

Rheumatoid arthritis (RA) is driven by antigen-specific T cell responses targeting the joints. MacDonald et al.1 define the range of dendritic cell (DC) populations within joints of RA patients and highlight specific iDC3 and DC2 populations enriched in inflamed RA synovium that promote T cell activation as well as tolerogenic AXL+ DC2s in healthy synovium that are lost in RA.

Central tolerance restricts T cells that target self-antigens. In this issue of Immunity, Abdelfattah et al.1 describe a method to generate self-reactive T cell receptors (TCRs) by directed evolution of non-autoreactive TCRs to recognize self-antigen peptides and demonstrate potential for T cells engineered with such receptors in immunotherapy.

CD4+ T helper (Th) cell differentiation depends on regulatory networks that enforce lineage commitment while suppressing alternative fates. In a recent issue of Nature, Hou et al. reveal that calcitonin gene-related peptide (CGRP) directs Th1 commitment, highlighting neuro-immune crosstalk in T cell fate decisions.

Mast cells are regarded as effectors in immune defense against parasites and venoms and play an essential role in the pathology of allergic diseases. More recently, mast cells have been shown to receive stimuli derived from type 2 immunity, tissue damage, stress, and inflammation. Mast cells then rapidly convert these diverse signals into appropriate, organ-specific protective reflexes that can limit

(Immunity 57, 2651–2668.e1–e12; November 12, 2024)

Many promising targets for adoptive T cell therapy (ACT) are self-antigens, but self-reactive T cells are generally eliminated during thymic selection or diverted to regulatory phenotypes. To bypass T cell tolerance and obtain potent and safe T cell therapeutics, we developed T-Switch, an in vitro T cell receptor (TCR) engineering platform for the creation, modification, and comprehensive profiling

Several recent studies have demonstrated that B cell-targeting chimeric antigen receptor (CAR) T cells offer a viable treatment option for patients with autoantibody-mediated autoimmune diseases. In this report, we summarize recent findings and key developments that were presented at the “1st International Autoimmune CAR T Innovators Summit” in Grassau, Germany.