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Mechanisms promoting epithelial regeneration after intestinal injury are poorly understood. Here, authors report that intestinal stem cells produce IL-33 after radiation injury, which induces Paneth cells to produce EGF and promote regeneration.

Zeiser and colleagues show that CAR T cell therapy results in upregulation of the TGFβ-activated kinase-1 (TAK1)–NF-κB–p38 MAPK pathway in microglia, causing neurocognitive defects, and find that TAK1 inhibition can reduce immune effector cell-associated neurotoxicity syndrome.

Follicular regulatory T (Tfr) cells modulate germinal center T and B cell responses, but how Tfr may control allograft rejection is still unclear. Here the authors show, using mouse kidney allograft rejection models, that Tfr suppresses the production of pro-inflammatory cytokines and alloreactive antibodies from alloreactive B cells to dampen graft rejection

The lymphotoxin (LT) system has several defined roles in the regulation of immunity as well as vascular and lymphatic biology, however its role in cancer is less understood. Here the authors show that regulatory T cell-derived LTα1β2 promotes LTβ receptor-nonclassical NFκB signaling in tumor cells and lymphatic endothelial cells, accelerating tumor growth and metastasis.

Signaling and transcriptional regulation of MDSC activity remains largely undefined. Here the authors show that monocytic MDSC immunosuppression is triggered by c-FLIP and requires NFκB, implicate this axis in cancer prognosis and response to therapy, and employ ectopic FLIP to treat immunopathology.

Steroid-refractory acute graft-versus-host disease (aGVHD) is associated with a low one-year survival rate. Here, the authors show that ROCK1 is upregulated in leukocytes from patients with steroid-refractory aGVHD and that ROCK1/2 inhibition reduces the severity of aGVHD in mice by interfering with activation of multiple immune cell types.

The Programmed death-1 (PD-1) and its ligand PD-L1 are critical checkpoints in the regulation of immune responses. Here the authors implicate PD-L1 signalling at lymphatic endothelium in the regulation of transendothelial migration of T cells.

Obesity promotes tumor growth yet simultaneously increases susceptibility to PD-1-targeted cancer immunotherapy.

Oncogenic Ras mutations are common drivers in myeloid leukemia. Here, the authors show in patient cells and in mice that oncogenic K-Ras activates NLRP3 inflammasome to drive myeloproliferation, which can be reversed by genetic or pharmacologic NLRP3 blockade.

The immunosuppressive tumor environment and the lack of functional anti-tumor immunity are major limiting factors in immunotherapy. Here the authors show that human and mouse tumors are infiltrated by virus-specific memory T cells, which can be harnessed by viral peptides to induce local and systemic anti-tumor immunity and synergize with checkpoint blockade.

Here, the authors review the most promising strategies for preventing or treating graft-versus-host disease after allogeneic haematopoietic stem cell transplantation. Approaches that target alloreactive T cells are often favoured, but those that exploit regulatory cell populations are now showing increasing success.

The precise role of follicular regulatory (T_FR) cells in the control of the germinal center (GC) reaction is unclear. Sage and colleagues develop a T_FR cell-deleter mouse that allows specific temporal deletion and show that T_FR cells primarily control early but not late GC responses.

Foxo proteins are required for maintaining T cell quiescence. Turka and colleagues use a constitutively active Foxo1 in T_reg cells to show that its downregulation is essential for maintaining their fitness in a competitive environment.

Lymphotoxin regulates lymphoid organ architecture and adhesion molecules involved in lymphocyte trafficking. Here the authors show that lymphotoxin produced by regulatory T cells promotes their migration to the draining lymph nodes by engaging its cognate receptor on lymphatic endothelial cells.

The transcription factor Foxp3 and Stat5 modulate lineage stability and function of regulatory T (Treg) cells to promote immune homeostasis. Here the authors show that O-GlcNAcylation of Foxp3 and Stat5, mediated by O-GlcNAc transferase (OGT), is essential for Treg-mediate immune balance, with Treg-specific deficiency of OGT leading to severe autoimmunity.

Combining the kinase inhibitor sorafenib with allogeneic stem cell transplantation boosts immune responses against a subtype of acute myelogenous leukemia, suggesting potential clinical benefit.

The DNA-binding factor SATB1 is known as a chromatin organizer. Schultze and colleagues show regulation of SATB1 expression by the transcription factor Foxp3 is necessary to confer suppression of effector cell activity.

A group of experts suggests ways in which deep learning can be used to enhance the potential for discovery in multi-messenger astrophysics.

Recent advances in the techniques for genetically engineering various lymphocyte subsets hold great promise for cell-based therapies to improve or correct aberrant immune responses. With several new approaches now entering clinical trials, continued efforts will focus on improving their safety and efficacy.

Activation of P2RX7 receptors by extracellular ATP is required for the generation, maintenance and function of central and tissue-resident CD8⁺ memory T cells.

Leukaemic stem cells in acute myeloid leukaemia are defined by a lack of expression of NKG2D ligands, which mediates their ability to evade surveillance by NK cells.

Haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for several haematological malignancies. Improvements in HSCT methodologies have considerably reduced treatment-related morbidity and mortality, thus broadening eligibility and placing increased emphasis on the prevention of disease relapse. In this Review, the authors discuss approaches to dissecting the biology of HSCT and exploiting the biological insights to enhance the graft-versus-tumour response, in particular with adoptive cell therapies and other immune-directed therapies, whilst minimizing graft-versus-host disease.

Therapeutic administration of highly selective ROCK2 inhibitor reverses established liver fibrosis induced by chemical injury combined with high fat diet in mice via concurrent targeting of inflammatory, fibrotic and metabolic cellular pathways