Deconstruction and reconstruction of lymphocytes for precision medicine.

Understanding fundamental lymphocyte biology and developing innovative strategies to harness lymphocytes to treat human diseases were the themes of the first SMART Symposium in Immunology held in March 2025 in Shenzhen, China.

Enantiomer-dependent and modification-free DNA matrix as an adjuvant for subunit vaccines against SARS-CoV-2 or pneumococcal infections.

The emergence of novel infectious disease has intensified demand for more advanced vaccine development and more potent adjuvants to enhance immunogenicity. Here we introduce a dynamic DNA supramolecular matrix assembled from five unmodified, short DNA single strands, serving as a safe, multifaceted adjuvant platform. This DNA matrix elicits a robust humoral response with minimal adverse effects, generating potent neutralizing antibodies and conferring robust protection against SARS-CoV-2 and Streptococcus pneumoniae infections.

Extended exergy accounting of agricultural resources in China's four provinces of mountains and rivers.

The agricultural sector in China has to balance resource investment, environmental emissions and yields to satisfy the high dietary demands of the population. In this study, extended exergy accounting (EEA) was conducted to analyse the usefulness of resources invested in agriculture and the yields of strategic importance to China in Hebei, Shanxi, Shandong and Henan (four provinces of mountains and rivers) in 2017 from a thermodynamics perspective. The fluxes resources of energy, materials, environmental emissions, labour, capital and yields were measured in joules.

CCR5-mediated dynamic maintenance of resident memory T cells in the respiratory tract.

Tissue-resident memory T cells (T) play a key role in defense against pathogen invading barrier sites and other non-lymphoid tissues. How T cells are maintained in various tissues, and how they relate to antigen-experienced memory T cells in lymphoid organs are not fully understood. By barcode-based lineage tracing and single-cell transcriptome analysis, we found a distinct population of CD69CD103 virus-specific CD8 T cells in draining lymph nodes (dLNs) following intranasal influenza infection.

Cholinergic regulation of thymocyte negative selection.

The immune and nervous systems use a common chemical language for communication, namely, the cholinergic signaling involving acetylcholine (ACh) and its receptors (AChRs). Whether and how this language also regulates the development of the immune system is poorly understood. Here, we show that mouse CD4CD8 double-positive thymocytes express high levels of α9 nicotinic AChR (nAChR) and that this receptor controls thymic negative selection.

An interleukin-9-ZBTB18 axis promotes germinal center development of memory B cells.

Memory B cell (MBC) development from germinal centers (GCs) entails profound changes in cell cycling, localization, and survival. Here, we examined the mechanisms that induce the memory program, focusing on interleukin (IL)-9, given its importance for normal recall antibody responses. Using adoptive transfer and radiation chimera models, we found that T cell-derived IL-9 was required for MBC development and function.

Bi-directional communication between intrinsic enteric neurons and ILC2s inhibits host defense against helminth infection.

Emerging studies reveal that neurotransmitters and neuropeptides play critical roles in regulating anti-helminth immune responses, hinting at the potential of intrinsic enteric neurons (iENs) in orchestrating intestinal immunity. Whether and how iENs are activated during infection and the potential neuroimmune interactions involved remain poorly defined. Here, we found that helminth infection activated a subset of iENs.

GZMK-expressing CD8 T cells promote recurrent airway inflammatory diseases.

Inflammatory diseases are often chronic and recurrent, and current treatments do not typically remove underlying disease drivers. T cells participate in a wide range of inflammatory diseases such as psoriasis, Crohn's disease, oesophagitis and multiple sclerosis, and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence, in part by forming persistent pathogenic memory. Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities.

Progressive polyadenylation and m6A modification of Ighg1 mRNA maintain IgG1 antibody homeostasis in antibody-secreting cells.

Antigen-specific antibodies are generated by antibody-secreting cells (ASCs). How RNA post-transcriptional modification affects antibody homeostasis remains unclear. Here, we found that mRNA polyadenylations and N6-methyladenosine (m6A) modifications maintain IgG1 antibody production in ASCs.

Single-chain A35R-M1R-B6R trivalent mRNA vaccines protect mice against both mpox virus and vaccinia virus.

Background: Mpox has spread to many countries around the world. While the existing live attenuated mpox vaccines are effective, advances in 21st century technologies now enable the development of vaccines with more specific antigens, clearer mechanisms, and more controllable side effects.

Methods: We systematically evaluated the immunogenicity and protective efficacy of the A35R, M1R and B6R antigens of the mpox virus (MPXV).

Epigenetic recording of stimulation history reveals BLIMP1-BACH2 balance in determining memory B cell fate upon recall challenge.

Memory B cells (MBCs) differentiate into plasma cells (PCs) or germinal centers (GCs) upon antigen recall. How this decision is programmed is not understood. We found that the relative strength between two antagonistic transcription factors, B lymphocyte-induced maturation protein 1 (BLIMP1) and BTB domain and CNC homolog 2 (BACH2), progressively increases in favor of BLIMP1 in antigen-responding B cells through the course of primary responses.

High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function.

Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses.

Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients.

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis.

B cell-reactive triad of B cells, follicular helper and regulatory T cells at homeostasis.

Autoreactive B cells are silenced through receptor editing, clonal deletion and anergy induction. Additional autoreactive B cells are ignorant because of physical segregation from their cognate autoantigen. Unexpectedly, we find that follicular B cell-derived autoantigen, including cell surface molecules such as FcγRIIB, is a class of homeostatic autoantigen that can induce spontaneous germinal centers (GCs) and B cell-reactive autoantibodies in non-autoimmune animals with intact T and B cell repertoires.

Foxp3-mediated blockage of ryanodine receptor 2 underlies contact-based suppression by regulatory T cells.

The suppression mechanism of Tregs remains an intensely investigated topic. As our focus has shifted toward a model centered on indirect inhibition of DCs, a universally applicable effector mechanism controlled by the transcription factor forkhead box P3 (Foxp3) expression has not been found. Here, we report that Foxp3 blocked the transcription of ER Ca2+-release channel ryanodine receptor 2 (RyR2).

Intranasal influenza-vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response in hamsters.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and "anatomical escape" characteristics threaten the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. Here we investigate immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants in hamsters.

A role for in constraining germinal center B cell formation.

Germinal center is a transient lymphoid tissue structure in which B cells undergo affinity maturation and differentiate into memory B cells and plasma cells. GC formation depends on B cell expression of BCL6, a master transcription regulator of the GC state. Bcl6 expression is under elaborate control by external signals.

Two-photon synthetic aperture microscopy for minimally invasive fast 3D imaging of native subcellular behaviors in deep tissue.

Holistic understanding of physio-pathological processes requires noninvasive 3D imaging in deep tissue across multiple spatial and temporal scales to link diverse transient subcellular behaviors with long-term physiogenesis. Despite broad applications of two-photon microscopy (TPM), there remains an inevitable tradeoff among spatiotemporal resolution, imaging volumes, and durations due to the point-scanning scheme, accumulated phototoxicity, and optical aberrations. Here, we harnessed the concept of synthetic aperture radar in TPM to achieve aberration-corrected 3D imaging of subcellular dynamics at a millisecond scale for over 100,000 large volumes in deep tissue, with three orders of magnitude reduction in photobleaching.

Different effects of vaccine on VST in critical and non-critical COVID-19 patients: A retrospective study of 363 cases.

Aim: To explore the risk factors of prolonged viral shedding time (VST) in critical/non-critical COVID-19 patients during hospitalization.

Methods: In this retrospective study, we enrolled 363 patients with SARS-CoV-2 infection admitted in a designated hospital during the COVID-19 outbreak in Nanjing Lukou International Airport. Patients were divided into critical (n = 54) and non-critical (n = 309) groups.

Germinal center reaction and output: recent advances.

The germinal center (GC) reaction is unique in that it incorporates clonal expansion, somatic mutagenesis, affinity-based selection, and differentiation events all in one tightly packed but highly dynamic microenvironment to produce affinity-matured plasma cells (PCs) or memory B cells (MBCs). Here, we review recent advances in our understanding of how cyclic expansion and selection are orchestrated, how stringency and efficiency of selection are maintained, and how external signals are integrated in B cells to promote post-GC development of PCs and MBCs.