Volume 24 Issue 1, January 2023

Diverse inflammasome stimuli recruit NLRP3 to dysfunctional endosomes via interactions with lipids that accumulate in excess on these organelles. Excess lipid detection may be a common principle that explains NLRP3 function in health and disease.

Interactions between the T cell co-receptors CD4 or CD8 and the kinase Lck safeguard T cell activation by low-affinity ligands. Meanwhile, ‘free’ Lck — which cannot bind co-receptors — elicits efficient anti-viral and anti-tumor responses by CD8⁺ T cells in vivo.

Signaling via T cell antigen receptors is diminished during aging. But paradoxically, CD4⁺ T cells from older adults tend to differentiate into effector-like rather than memory cells. An altered balance between the activities of HELIOS, IL-2Rα, and STAT5 influences this decision.

Expression of the inhibitory receptor PD-1 on regulatory T cells in the tumor microenvironment provides intrinsic stabilization, proliferation and metabolic rewiring signals to restrain tumor immunity.

Aging is commonly associated with the loss of cognitive capacity driven by the degeneration of the brain. New research strengthens the links between CD8⁺ T cells and interferon-γ production in the brain, and neurodegeneration.

On 15–16 June 2022, the National Institute of Allergy and Infectious Diseases hosted a virtual workshop on the topic of T cell technologies to discuss assays, novel technology development, bench and clinical application of those technologies, and challenges and innovations in the field.

Kuchroo and colleagues review T_H17 cell heterogeneity and discuss how this affects the function of T_H17 cells in homeostasis and disease.

A dogma in the inflammasome field is that NLRP3 activation occurs at dispersed vesicles of the trans-Golgi network. Here, Ricci and colleagues find that these vesicles are of endosomal origin and that endosomes comprise the compartment where NLRP3 is activated.

Henao-Mejia and colleagues provide a detailed characterization of the 3D genome architecture of ILCs and demonstrate that ILC2 development and progression of allergic inflammation are controlled by a unique 3D DNA topology at the Id2 locus.

Boussiotis and colleagues show that the tyrosine phosphatase SHP-2 regulates the differentiation and antitumor function of monocytes downstream of the inhibitory PD-1 receptor.

Modeling a rare bone marrow failure disorder due to haploinsufficiency for the MECOM transcription factor identifies a human hematopoietic stem cell regulatory network, which is co-opted by high-risk leukemias.

The factors controlling monocyte fate commitment toward macrophages versus dendritic cells are unclear. Here the authors show that ETV3 and ETV6 enable dendritic cell differentiation by repressing the macrophage transcriptional program.

Goronzy and colleagues examine differences in naive CD4⁺ T cells from young and older adults to TCR stimulation. They find reduced HELIOS expression in the elderly, resulting in increased CD25 expression and activation of pSTAT5 in FOXP3⁻ T cells. This scenario favors generation of short-lived effector T cells over memory cell populations.

De Jong and colleagues identify staphylococcal phosphatidylglycerol lipids as antigens for human CD1a-restricted T cells, which promote type 2 immune responses and may contribute to atopic dermatitis.

Gata3 upregulation is required for T_H2 cell polarization. McKenzie and colleagues find that integrin αvβ3 is upregulated by Gata3 and that this is crucial in inducing FAK–mTOR signaling required for T_H2 cell differentiation.

Weiss and colleagues identify a role for the endoplasmic reticulum-tethered PI transfer protein Nir3 in replenishing plasma membrane PIP2 levels in DN3-DP thymocytes, thereby increasing the sensitivity of developing thymocytes to weak TCR agonists.

Ha and colleagues show that loss of PD-1 expression on regulatory T cells in the tumor environment reduces their metabolic fitness and proliferative capacity.

Ammonia detoxification is generally thought to occur exclusively in the liver. Here the authors show that ammonia detoxification via the urea and citrulline cycles is utilized by memory CD8⁺ T cells to maintain the longevity.

Stepanek and colleagues demonstrate that the LCK kinase associated with CD4 or CD8 co-receptors has kinase-dependent and kinase-independent roles in T cell activation.

Manthiram and colleagues analyze the peripheral blood, tonsils and adenoids in children undergoing tonsillectomy or adenoidectomy and find evidence of continued tissue-specific immunity to SARS-CoV-2 and viral RNA persistence weeks to months after acute infection.