Large-scale autoantibody profiling reveals pathogenic anti-IL-1RA autoantibodies that disrupt placental vascular integrity and are associated with preterm birth, linking maternal humoral immunity to inflammatory pregnancy complications.
A preprint by Nah et al. reports that PD-L1 and PD-L2 on dendritic cells in the tumour versus tumour-draining lymph nodes have spatially regulated effects on the antitumour T cell response.
Pain is profoundly shaped by neuroimmune interactions within peripheral tissues. Nociceptors are specialized sensory neurons that express receptors for cytokines, lipid mediators, complement components, antibodies and microbial signals, enabling immune mediators to directly modulate neuronal excitability. In turn, nociceptors influence immune cell and stromal cell activity through the release of neuropeptides and cytokines. Some of these pathways are shared across multiple tissues in pathological pain states, whereas others reflect the distinct immune and stromal environments of the skin, joints, muscles, gut, peripheral nerves, sensory ganglia and meninges. Across these sites, immune-to-neuron signalling orchestrates the initiation and amplification of pain, while maladaptive feedback loops reinforce hypersensitivity. In concert, coordinated neuroimmune signalling also contributes to pain resolution by restoring homeostasis. Emerging human studies reveal convergent neuroimmune signatures across nociceptive, neuropathic and nociplastic pain conditions, underscoring their translational relevance. By integrating both shared mechanisms and tissue-specific mechanisms, this Review highlights how peripheral neuroimmune crosstalk shapes pain across diverse contexts. Furthermore, it outlines therapeutic opportunities to rebalance these pathways, offering prospects for durable and mechanism-based analgesia. This Review explores how neuroimmune crosstalk shapes pain responses. The authors describe the interactions between nociceptors and immune cells across different anatomical sites and discuss emerging therapeutic strategies for pain management.
Cytotoxic CD8+ T cells induce target-cell death by producing effector proteases called granzymes. Most granzymes, as exemplified by granzyme B, induce apoptosis by cleaving intracellular substrates after delivery to target cells via the immunological synapse. By contrast, it was recently shown that granzyme K (GZMK), which is selectively expressed by a unique population of CD8+ T cells, activates the complement cascade instead of executing direct cytotoxicity. In this Perspective, we summarize recent data on complement activation by CD8+ T cell-derived GZMK that points to a novel lymphocyte-mediated pathway of complement activation. We present evidence that GZMK-expressing CD8+ T cells have distinct pro-inflammatory effects in tissues and discuss their involvement in an array of chronic and inflammatory diseases. Furthermore, we propose the concept of ‘tissue histotoxicity’ as a core feature of GZMK-expressing CD8+ T cells. We suggest this as a defence strategy that enables the immune system to act on a tissue neighbourhood instead of targeting one cell at a time. Finally, we discuss the possibility of GZMK expression being a heritable trait in subsets of memory T cells. This Perspective discusses the emerging biology of a unique population of granzyme K-expressing CD8+ T cells. Unlike canonical cytotoxic CD8+ T cells, which mediate direct cell killing, granzyme K-expressing CD8+ T cells activate the complement cascade and promote localized tissue inflammation. The authors propose that such ‘tissue histotoxicity’ is an important defence strategy, allowing CD8+ T cells to target a tissue neighbourhood instead of one cell at a time.
A preprint by Kazane et al. reports a role for the histone methytransferase KMT2D in controlling the secretory function of natural killer cells.
