Churmy Y. Fan and al.

The authors of this study investigated the role of pannexin-1 (Panx1) in a murine model of mechanical allodynia in both males and females. In males, Panx1 stimulates the release of VEGF-A by microglia and either a microglial knockdown of Panx1 or a pharmacological blockade of the VEGF receptor attenuates allodynia. In females, nerve injury is associated with the intramedullar recruitment of CD8+ T lymphocytes along with a local increase of leptin levels. The release of leptin by CD8+ T cells is Panx1-dependent, and intrathecal injection of a leptin-neutralizing antibody prevents allodynia in females but not males. The authors conclude that targeting Panx1 could alleviate allodynia in both sexes, whereas therapies targeting T cells and/or leptin may only be effective in females.

Miguel Marin-Rodero and al.

This study highlights the heterogeneity of meningeal regulatory T cells (Tregs). A subset of such Tregs specializes in controlling interferon-gamma (IFN-γ) responses and another is dedicated to regulating follicular B cell responses. Under Treg ablation, the authors report that meningeal lymphocytes secrete IFN-γ  and access to the brain parenchyma. In the meantime,the molecular profile of meningeal B cells is altered and, at distance, the hippocampus adopts a "reactive" state characterized by morphological and transcriptional changes in multiple glial cell types.

Yinsheng Wang and al.

Emerging studies reveal that neurotransmitters and neuropeptides play a key role in regulating anti-helminth immune responses, suggesting their potential to orchestrate intestinal immunity. However, little is known about how intrinsic enteric neurons (iENs) are activated during infection and the potential neuroimmune interactions involved. In this study, the authors show that in mice, helminth infection activates a subset of intrinsic enteric neurons (iENs). Single-cell RNA sequencing reveals alterations in the profile of intrinsic primary afferent neurons (IPANs) expressing the interleukin-13 receptor (IL-13R). In particular, an upregulation of the neuropeptide β-CGRP is observed. Using a combination of genetically modified mice and transfection tools, the authors demonstrate that ILC2-derived IL-13 is necessary for iEN activation via IL-13R and for β-CGRP production by iENs. In turn, β-CGRP inhibits ILC2 responses and anti-helminth immunity.

Jeffrey M. Grimes and al.

Oncolytic viruses (OVs) are considered a promising cancer immunotherapy. However, the long-term effects on tumor cells and their microenvironment, as well as the nature of post-therapy anti-tumor immunity, remain largely unknown. This study demonstrates that CD4+ T lymphocytes are essential for sustained tumor control in syngeneic murine models of glioblastoma treated with a modified oncolytic herpes simplex virus engineered to express interleukin-12 (IL-12). More specifically, the upregulation of major histocompatibility complex class II (MHCII) expression on residual tumor cells facilitates the development of CD4+ T cells, ensuring tumor control and memory responses.

Thomas Look and al.

Chimeric antigen receptor CAR T-cells are a promising cancer immunotherapy. However, other CAR-engineered cell types may also have therapeutic potential.This study compares the therapeutic effects of CAR T cells, CAR NK cells, and CAR macrophages in a murine glioblastoma model. In cell cultures, the authors show that CAR T cells effects of cancer cell survival are CAR-dependent, while NK cell cytotoxicity relies more on intrinsic properties than CAR signaling. Similarly, CAR macrophages exhibit their own distinct behavior. In orthotopic, immunocompetent glioma murine models, systemically administered CAR T cells accumulate more efficiently in the tumor, and each immune cell type induces distinct changes in the tumor microenvironment. However, irrespective of the CAR cell type considered, therapeutic efficacy is noticeably enhanced by the co-expression of pro-inflammatory cytokines in CAR immune cells.