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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.
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.
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.
The regulatory protein SREBP is required for CD8+ T cell metabolic reprogramming after activation. Luo et al. demonstrate that stimulated B cells require SCAP, a regulator of SREBP, for metabolic reprogramming and the formation and maintenance of germinal center B cells.
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.
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 TH2 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 TH2 cell differentiation.
Exhausted CD8+ T cells with diminished effector functions accumulate in tumors. Here, the authors show that hypoxia induces a suppressive phenotype in exhausted T cells and that interfering with hypoxia-mediated CD39 expression limits immunosuppression in the tumor and augments immunotherapy, resulting in arrest of tumor growth.
Cancer immunotherapies can be limited by terminally dysfunctional T cells in the tumor microenvironment. Here the authors present a model of stable human T cell dysfunction to show that TGFβ contributes to this terminal dysfunction which can be therapeutically inhibited by simultaneously blocking TGFβ1 and boosting bone morphogenetic protein (BMP) signaling.
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.
Betts and colleagues have developed a method for characterizing the HIV reservoir at the single-cell level to gain insight into the heterogeneous nature of CD4+ T cells harboring HIV-1 proviral DNA in patients undergoing antiretroviral treatment.
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.
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.
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.
Zhang et al. describe how meningeal MAIT cells maintain meningeal barrier integrity via the secretion of antioxidants, which also limit neuroinflammation and preserve spatial learning.
We isolated CD4+ T cell clones from healthcare workers infected with SARS-CoV-2 during the first COVID-19 wave and identified 21 epitopes across three viral proteins: spike, membrane and nucleoprotein. Focusing on spike protein, for seven of ten epitopes mutated in variants of concern, we found that T cell recognition was impaired.
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.
The fungal pathogen receptor dectin-1 instructs the development of non-pathogenic TH17 cells via TGFβ activation. This process requires strict control of the expression of type I interferon to ensure a delicate balance in the expression of its effector genes that control the release of active TGFβ.