A physiological perspective on neuroimmune tissue innervation. Daniel A Waizman

Trends Immunol. 2025 Jun 11:S1471-4906(25)00124-3. doi: 10.1016/j.it.2025.05.003. Online ahead of print. ABSTRACT Organisms must adapt to unpredictable environmental perturbations. We propose that the immune system, which can be redistributed across tissues (‘immune innervation’), cooperates with the nervous system to form a larger integrative network that can maximize the number of adaptive physiologic states to a … Read more

Restraining the killers: regulation of T cell quiescence. Molly E Lumnitzer

Trends Immunol. 2025 May 27:S1471-4906(25)00121-8. doi: 10.1016/j.it.2025.04.008. Online ahead of print. ABSTRACT Active regulation of T cell quiescence is important to sustain immune responses to vaccination and infection while preventing inappropriate responses such as autoimmunity. Recent studies highlight that quiescence in naïve T cells is actively regulated by transcription factors and tonic signaling. Loss of … Read more

Lactate trains immunity. Alba Llibre

Trends Immunol. 2025 May 26:S1471-4906(25)00123-1. doi: 10.1016/j.it.2025.05.002. Online ahead of print. ABSTRACT Understanding the mechanisms implicated in the establishment of trained immunity could aid the design of novel therapeutic approaches. By studying Bacille Calmette-Guerin (BCG) vaccination in a human cohort, Ziogas and colleagues demonstrate the role of lactate generation and its use for histone lactylation … Read more

Microglia replacement: from monocytic origin to therapy. Jingyi Yang

Trends Immunol. 2025 May 26:S1471-4906(25)00122-X. doi: 10.1016/j.it.2025.05.001. Online ahead of print. ABSTRACT Microglia replacement is reshaping neurodegenerative disease therapy, yet its key prerequisites remain unclear. In the current issue of Immunity, Aisenberg et al. and Bastos et al. reveal how developmental origin influences monocyte engraftment into the brain, and demonstrate the therapeutic potential of monocyte-based … Read more

YTHDF2: a key RNA reader and antitumor target. Sai Xiao

Trends Immunol. 2025 May 20:S1471-4906(25)00095-X. doi: 10.1016/j.it.2025.04.003. Online ahead of print. ABSTRACT N6-methyladenosine (m6A) is a key mRNA modification influencing mRNA stability and translation. YTHDF2, a major m6A ‘reader’, was initially recognized for promoting mRNA decay but is now also known to enhance translation by binding to methylated mRNAs. YTHDF2 maintains the function of immune … Read more

Evolutionarily ancient functions of enzymatic TIR proteins in innate immunity. Khursheed A Wani

Trends Immunol. 2025 May 19:S1471-4906(25)00116-4. doi: 10.1016/j.it.2025.04.005. Online ahead of print. ABSTRACT Proteins with a Toll/interleukin-1 receptor/resistance (TIR) domain are among the most ancient immune regulators and include well-known pattern recognition receptors (PRRs). A specialized subset of TIR domain proteins are enzymes that predominantly use nicotinamide adenine dinucleotide (NAD+) to generate second messenger metabolites. These … Read more

Causes and consequences of T cell DNA damage. Costas Koufaris

Trends Immunol. 2025 May 16:S1471-4906(25)00119-X. doi: 10.1016/j.it.2025.04.006. Online ahead of print. ABSTRACT Although DNA damage is a common cellular event, T cells experience significant genotoxic stresses because of rapid antigen-stimulated expansion and their presence in various nonlymphoid microenvironments. In addition to the well-established link between genomic instability and malignancy, recent genomic studies have uncovered a … Read more

Lung tumor immunity: redirecting macrophages through infection-induced inflammation. Öznur Aktay-Cetin

Trends Immunol. 2025 May 16:S1471-4906(25)00096-1. doi: 10.1016/j.it.2025.04.004. Online ahead of print. ABSTRACT Macrophages play a central role in maintaining tissue homeostasis and in surveillance against pathogens and disease. In the lung, they can adopt either proinflammatory or anti-inflammatory states depending on the nature of the stimulus. As the predominant immune cells in both the lung … Read more

Using TCR-CAR dual signaling for precise cancer targeting. Mohammad Shahbazy

Trends Immunol. 2025 May 13:S1471-4906(25)00120-6. doi: 10.1016/j.it.2025.04.007. Online ahead of print. ABSTRACT Recently, Kondo et al. engineered the coexpression of a T cell receptor (TCR) and a chimeric antigen receptor (CAR) and developed an antagonism-enforced braking system where TCR signals both enhance and inhibit CAR activation. This work may enable rational design of CAR-T agents … Read more

The microglial lineage: present and beyond. Wei-Wei Chen

Trends Immunol. 2025 May 13:S1471-4906(25)00093-6. doi: 10.1016/j.it.2025.04.001. Online ahead of print. ABSTRACT Emerging studies demonstrate the presence of cells with microglial features in peripheral tissues. Here, we propose using the term ‘microglial lineage’ to categorize both these cells and classical microglia. Microglial lineage cells are resident immune cells with a microglial molecular phenotype and ontogeny … Read more

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