GFI1B specifies developmental potential of innate lymphoid cell progenitors in the lungs.

Tissue-resident innate lymphoid cells (ILCs) play a vital role in the frontline defense of various tissues, including the lung. The development of type 2 ILCs (ILC2s) depends on transcription factors such as GATA3, RORα, GFI1, and Bcl11b; however, the factors regulating lung-resident ILC2s remain unclear. Through fate mapping analysis of the paralog transcription factors GFI1 and GFI1B, we show that GFI1 is consistently expressed during the transition from progenitor to mature ILC2s.

The CD8 T cell tolerance checkpoint triggers a distinct differentiation state defined by protein translation defects.

Peripheral CD8 T cell tolerance is a checkpoint in both autoimmune disease and anti-cancer immunity. Despite its importance, the relationship between tolerance-induced states and other CD8 T cell differentiation states remains unclear. Using flow cytometric phenotyping, single-cell RNA sequencing (scRNA-seq), and chromatin accessibility profiling, we demonstrated that in vivo peripheral tolerance to a self-antigen triggered a fundamentally distinct differentiation state separate from exhaustion, memory, and functional effector cells but analogous to cells defectively primed against tumors.

Indirect CD4 T cell protection against mouse gamma-herpesvirus infection via interferon gamma.

Unlabelled: CD4 T cells play a key role in γ-herpesvirus infection control. However, the mechanisms involved are unclear. Murine herpesvirus type 4 (MuHV-4) allows relevant immune pathways to be dissected experimentally in mice.

The transcription factor SpiB regulates the fibroblastic reticular cell network and CD8 T-cell responses in lymph nodes.

Fibroblastic reticular cells (FRCs) construct microanatomical niches that support lymph node (LN) homeostasis and coordination of immune responses. Transcription factors regulating the functionality of FRCs remain poorly understood. Here, we investigated the role of the transcription factor SpiB that is expressed in LN FRCs.

In situ single-cell profiling sheds light on IFI27 localisation during SARS-CoV-2 infection.

The utilization of single-cell resolved spatial transcriptomics to delineate immune responses during SARS-CoV-2 infection was able to identify M1 macrophages to have elevated expression of IFI27 in areas of infection.

Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

Objective: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear.

Faster Gastrointestinal Transit, Reduced Small Intestinal Smooth Muscle Tone and Dysmotility in the Mouse Model of Autism.

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the gene encoding the cell adhesion protein Neuroligin-3 was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction.

A centenary of service: 100 years of Immunology & Cell Biology.

This year marks the 100th year of the publication of Immunology & Cell Biology since it was first published in March 1924 as the Australian Journal of Experimental Biology and Medical Science. In this Editorial, we recount the journal from its founding, to its focus on immunology, through to the modern era.

Survival and division fate programs are preserved but retuned during the naïve to memory CD8 T-cell transition.

Memory T cells are generated from naïve precursors undergoing proliferation during the initial immune response. Both naïve and memory T cells are maintained in a resting, quiescent state and respond to activation with a controlled proliferative burst and differentiation into effector cells. This similarity in the maintenance and response dynamics points to the preservation of key cellular fate programs; however, whether memory T cells have acquired intrinsic changes in these programs that may contribute to the enhanced immune protection in a recall response is not fully understood.

TCF-1 limits intraepithelial lymphocyte antitumor immunity in colorectal carcinoma.

Intraepithelial lymphocytes (IELs), including αβ and γδ T cells (T-IELs), constantly survey and play a critical role in maintaining the gastrointestinal epithelium. We show that cytotoxic molecules important for defense against cancer were highly expressed by T-IELs in the small intestine. In contrast, abundance of colonic T-IELs was dependent on the microbiome and displayed higher expression of TCF-1/ and a reduced effector and cytotoxic profile, including low expression of granzymes.

A robust platform for integrative spatial multi-omics analysis to map immune responses to SARS-CoV-2 infection in lung tissues.

The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid and similar, but a robust platform for deep tissue characterization of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues.

The seductive allure of spatial biology: accelerating new discoveries in the life sciences.

Spatial biology is a rapidly developing field which enables the visualization of protein and transcriptomic data while preserving tissue context and architecture. Initially used in discovery, there is growing promise for translational and diagnostic assay developments. Immediate applications are in precision medicine, such as being able to match patients to optimal therapies through better understanding the tumor microenvironment.

transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study.

Purpose: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients.

Gutsy sensations modulate intestinal disease.

Pain is a hallmark symptom associated with intestinal inflammation. Two related articles published in Cell by Zhang et al. and by Yang et al.

Innate lymphoid cells: potential targets for cancer therapeutics.

Innate lymphoid cells (ILCs) comprise a number of different subsets, including natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue-inducer (LTi) cells that express receptors and signaling pathways that are highly responsive to continuously changing microenvironmental cues. In this Review, we highlight the key features of innate cells that define their capacity to respond rapidly to different environments, how this ability can drive both tumor protection (limiting tumor development) or, alternatively, tumor progression, promoting tumor dissemination and resistance to immunotherapy. We discuss how understanding the regulation of ILCs that can detect tumor cells early in a response opens the possibility of exploiting this functional plasticity to develop rational therapeutic strategies to bolster adaptive immune responses and improve patient outcomes.

Metabolic features of innate lymphoid cells.

Innate and adaptive immune cells are found in distinct tissue niches where they orchestrate immune responses. This requires intrinsic and temporal metabolic adaptability to coordinately activate the immune response cascade. Dysregulation of this program is a key feature of immunosuppression.

Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes that govern this remain unknown.

The unique role of innate lymphoid cells in cancer and the hepatic microenvironment.

Cancer is a complex disease, and despite incredible progress over the last decade, it remains the leading cause of death worldwide. Liver cancers, including hepatocellular carcinoma (HCC), and liver metastases are distinct from other cancers in that they typically emerge as a consequence of long-term low-grade inflammation. Understanding the mechanisms that underpin inflammation-driven tissue remodeling of the hepatic immune environment is likely to provide new insights into much needed treatments for this devastating disease.

ZBTB46 in ILC3: shared transcriptional infrastructure defines gut-protective capabilities.

Group 3 innate lymphoid cells (ILC3s) are distributed along the gastrointestinal tract at the interface between the immune system and the gut lumen, which carries a significant microbial burden. In a new study, Zhou et al. investigated the expression of transcription factor ZBTB46, normally thought to be restricted to classical dendritic cells (cDCs), and discovered that ZBTB46 expression by ILC3s in the mouse colon forms an essential part of the gastrointestinal armory to calibrate inflammatory responses.