Volume 24 Issue 2, February 2023

T_H17 cells combat infection but can also drive pathological inflammation. A T_H17 cell NLRP3–caspase-8–caspase-3–GSDME axis is now shown to release the alarmin IL-1α without triggering cell death.

In addition to the acute phase of SARS-CoV-2 infection, a significant percentage of patients experience a prolonged illness with varying symptomatology. Longitudinal SARS-CoV-2 patient-centric immunologic, inflammatory and metabolic data collection has allowed the generation of a composite signature to predict recovery.

Human resident memory T (T_RM) cells clonally segregate in distinct tissues, with gene expression signatures tailored to those sites. Hence, beyond a shared language of residency, T_RM cells may acquire local dialects to provide site-specific immunity.

A specialized subset of iNKT cells populates the skin in early life, where their supply of transferrin regulates iron metabolism to promote hair follicle development.

Starting on 19 September 2022, the very first ImmunOctoberfest conference took place in Raitenhaslach, Germany, bringing together scientists from all over the world to discuss ‘bridging innovation and translation in T cell immunotherapy’.

Sterol regulatory element-binding protein (SREBP) signaling regulates cellular lipid homeostasis. We discovered that SREBP signaling in B cells is crucial for antibody responses and the generation of germinal centers and B cell memory compartments in response to vaccination. These results provide mechanistic insights that couple sterol metabolism to the quality and longevity of humoral immunity.

Exhausted effector T cells accumulate in tumors and are the intended targets of cancer immunotherapy. New data suggest that upon infiltration and subsequent exhaustion in the tumor microenvironment, these T cells can take on an immunosuppressive function — and work against the immune response to cancer.

Schwartz et al. propose that the antiviral type I interferon response in the brain’s choroid plexus might lead to cognitive sequelae in COVID-19.

Here, the authors show that a subset of NKT2 cells are programmed during thymic development at early postnatal ages to migrate to the skin, where they support local tissue homeostasis through regulation of iron metabolism.

Trained immunity can manifest as a form of innate immune memory whereby innate immune cell responses are reprogrammed to respond differently to a variety of stimuli. Here, the authors show that lung macrophages can be trained by whole beta-glucan particle to enhance their ability to control tumor metastasis.

Caligiuri and colleagues show that the m⁶A reader YTHDF2 modulates the inflammatory activation and antitumor function of tumor-associated macrophages in part by modulating the stability of Stat1 mRNA.

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.

Gasdermin E pore formation has been associated with pyroptotic cell death. Here the authors identify gasdermin E pores in a subset of human T_H17 cells and show that rather than killing these cells the pores enable the release of IL-1α on NLRP3 inflammasome activation as an antifungal immune response.

Farber and colleagues examine the phenotypic, transcriptomic, clonal, and functional differences between tissue-resident T cells in various barrier tissue sites relative to T cells in lymphoid organs and circulation in humans.

Murre and colleagues identify a specific enhancer, E34, within the Igk locus that is required for chromatin remodeling and repositioning to promote Rag-mediated Igkv7-33 V_κ-J_κ gene recombination, needed for generation of anti-phosphorylcholine-specific antibodies. Mice lacking E34 are more susceptible to Streptococcus pneumoniae infections.

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.

Ruffieux, Hess and colleagues analyze longitudinal phenotyping of patients with coronavirus disease 2019 to show that covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites influence the restoration of homeostasis, the risk of death and that of long COVID.

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.