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The spleen is a vital organ for the immune system, while splenectomy may be necessary for various reasons. However, there is limited research on the impact of splenectomy on T cell function in peripheral lymph nodes as a compensatory mechanism in preventing infections. This study aimed to investigate the characteristics and function of CD8+ and CD4+ T cells in different peripheral lymph nodes during viral infection using a well‐established splenectomy model. The results revealed that splenectomy caused an increase in CD8+GP33+ T cells in the mesenteric lymph nodes (MLN). Moreover, we demonstrated that splenectomy resulted in an increase of effector KLRG1+ T cells in the MLN. Additionally, the number of CD4+ cytotoxic T cells (CD4 CTLs) was also elevated in the peripheral lymph nodes of mice with splenectomy. Surprisingly, aged mice exhibited a stronger compensatory ability than adult mice, as evidenced by an increase in effector CD8+ T cells in all peripheral lymph nodes. These findings provide compelling evidence that T cells in MLN play a crucial role in protecting individuals with splenectomy against viral infections. The study offers new insights into understanding the changes in the immune system of individuals with splenectomy and highlights the potential compensatory mechanisms involved by T cells in peripheral lymph nodes. [ABSTRACT FROM AUTHOR]

Cancer photo‐immunotherapy (CPIT) as an ideal strategy can rapidly release hostile signals by appropriate dosage of focal laser irradiation to unmask primary tumor immunogenicity and can activate adaptive immunity to control distant metastases. However, many factors, including disordered immunometabolism, poor penetration of photothermal agents and immuno‐regulators, inadequate laser penetration into the deep tumor region, restrict the therapeutic outcomes of CPIT. Here, a second near‐infrared window (NIR‐II) photo‐immunometabolic cancer therapy (PICT) by a programmed raspberry‐structured nanoadjuvant (PRNMT) is presented that can potentiates efficient immunogenic cell death (ICD) in deep tumor tissue and alleviates immunometabolic disorder. The PRNMT is architected through self‐assembly of indoleamine 2,3‐dioxygenase 1 (IDO‐1) inhibitor modified small‐sized CuS nanoparticles (CuS5) and tumor microenvironment (TME) responsive cationized polymeric matrix. The TME can trigger the splitting and surface cationization of PRNMT into small cationized CuS5 that feature high transcytosis potential and TME immunometabolic regulation. Upon NIR‐II irradiation, CuS5 induce homogeneous ICD and release immunometabolic regulator in deep tumor tissues, which ameliorates IDO‐1 mediated immunometabolic disorder and further suppresses regulatory T cells infiltration. PRNMT mediated PICT effectively delays the primary murine mammary carcinoma 4T1 tumor growth and inhibits the lethal pulmonary metastasis in combination with programmed cell death protein 1 (PD1) blockade. [ABSTRACT FROM AUTHOR]

Dysregulation of auto-reactive T cells and autoantibody-producing B cells and excessive inflammation are responsible for the occurrence and development of autoimmune diseases. The suppression of autoreactive T cell activation and autoantibody production, as well as inhibition of inflammatory cytokine production have been utilized to ameliorate autoimmune disease symptoms. However, the existing treatment strategies are not sufficient to cure autoimmune diseases since patients can quickly suffer a relapse following the end of treatments. Pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), Nod-like receptors (NLRs), RIG-I like receptors (RLRs), C-type lectin receptors (CLRs) and various nucleic acid sensors, are expressed in both innate and adaptive immune cells and are involved in the development of autoimmune diseases. Here, we have summarized advances of PRRs signaling pathways, association between PRRs and autoimmune diseases, application of inhibitors targeting PRRs and the corresponding signaling molecules relevant to strategies targeting autoimmune diseases. This review emphasizes the roles of different PRRs in activating both innate and adaptive immunity, which can coordinate to trigger autoimmune responses. The review may also prompt the formulation of novel ideas for developing therapeutic strategies against autoimmune diseases by targeting PRRs-related signals. [ABSTRACT FROM AUTHOR]

Early T‐cell development from CD4− CD8− double‐negative (DN) stage to CD4+ CD8+ double‐positive (DP) stage in the thymus is regulated through multiple steps involving a batch of sequentially expressed factors. Our preliminary data and a recent report showed that AT‐rich interaction domain 1A (Arid1a) is required for the transition from DN to DP stages, but the mechanism is not fully understood. In this study, we consolidated that conditional deletion of Arid1a in T‐cell lineage intrinsically caused developmental blocks from DN3 to DN4 stages, as well as from DN4 to DP stages using both in vivo adoptive T‐cell transfer model and in vitro culture system. The expression of intracellular TCRβ is significantly decreased in Arid1a‐deficient DN4 cells compared with WT cells. OT1 transgenic TCR can rescue the defect in the transition from DN3 to DN4 stages, but not from DN to DP stages. Furthermore, we observed a comparable or stronger proliferation capacity accompanied by a significant increase in cell death in Arid1a−/− DP cells compared with that in WT controls. RNA‐Seq analysis shows a significant enrichment of apoptotic pathway within differentially expressed genes between Arid1a−/− and WT DP cells, including the upregulation of Bim, Casp3 and Trp53 and the downregulation of Rorc, Bcl‐XL and Mcl1. Therefore, our study reveals a novel mechanism that Arid1a controls early T‐cell development by maintaining intracellular TCRβ expression‐mediated β‐selection and activating parallel cell survival pathways. [ABSTRACT FROM AUTHOR]

Under steady‐state conditions, the pool size of peripheral CD8+ T cells is maintained through turnover and survival. Beyond TCR and IL‐7R signals, the underlying mechanisms are less well understood. In the present study, we found a significant reduction of CD8+ T cell proportion in spleens but not in thymi of mice with T cell‐specific deletion of Mediator Subunit 1 (Med1). A competitive transfer of wild‐type (WT) and Med1‐deficient CD8+ T cells reproduced the phenotype in the same recipients and confirmed intrinsic role of Med1. Furthermore, we observed a comparable degree of migration and proliferation but a significant increase of cell death in Med1‐deficient CD8+ T cells compared with WT counterparts. Finally, Med1‐deficient CD8+ T cells exhibited a decreased expression of interleukin‐7 receptor α (IL‐7Rα), down‐regulation of phosphorylated‐STAT5 (pSTAT5) and Bim up‐regulation. Collectively, our study reveals a novel role of Med1 in the maintenance of CD8+ T cells through IL‐7Rα/STAT5 pathway‐mediated cell survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune cells can be powerful regulators of tumor growth and disease progression. Yet, the potential role of professional antigen-presenting cells in soft tissue sarcoma is poorly explored. Both dendritic cells and macrophages may present exogenous antigens through major histocompatibility complex (MHC) class I molecules to CD8+ T cells, a process referred to as cross presentation. With the concept of cellular cross presentation in mind, the present study supports the hypothesis that CD11c+ cells in direct cell-cell contact with CD8+ T cells within the primary tumor are associated with an active anti-tumor immune microenvironment and favorable prognosis. Our work hereby defines a novel biomarker for immune surveillance where presence of spatial cross presentation at tissue level resolution is significantly associated with overall survival. Importantly, this biomarker is independent from established prognostic markers like tumor grade. Biomarkers linked to immune surveillance are expected to gain increasing attention with the advent of immunotherapy in clinical practice. Checkpoint inhibitors are slowly being introduced in the care of specific sarcoma subtypes such as undifferentiated pleomorphic sarcoma, alveolar soft part sarcoma, and angiosarcoma even though formal indication is lacking. Proper biomarkers to unravel potential immune reactivity in the tumor microenvironment are therefore expected to be highly warranted. In this study, intratumoral spatial cross presentation was investigated as a novel concept where immune cell composition in the tumor microenvironment was suggested to act as a proxy for immune surveillance. Double immunohistochemistry revealed a prognostic role of direct spatial interactions between CD11c+ antigen-presenting cells (APCs) and CD8+ cells in contrast to each marker alone in a soft tissue sarcoma (STS) cohort of 177 patients from the Karolinska University Hospital (MFS p = 0.048, OS p = 0.025). The survival benefit was verified in multivariable analysis (MFS p = 0.012, OS p = 0.004). Transcriptomics performed in the TCGA sarcoma cohort confirmed the prognostic value of combining CD11c with CD8 (259 patients, p = 0.005), irrespective of FOXP3 levels and in a CD274 (PD-LI)-rich tumor microenvironment. Altogether, this study presents a histopathological approach to link immune surveillance and patient survival in STS. Notably, spatial cross presentation as a prognostic marker is distinct from therapy response-predictive biomarkers such as immune checkpoint molecules of the PD-L1/PD1 pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • Macrophages develop evolutionary versatility in expressed genes. • B cell immunity is relatively conserved among vertebrate species. • Compensatory TCR cascade components are utilized by different species. • Mouse species shows the highest similarity in immune transcriptomes to human among multiple vertebrates. Both innate and adaptive immune system undergo evolution from low to high vertebrates. Due to the limitation of conventional approaches in identifying broader spectrum of immune cells and molecules from various vertebrates, it remains unclear how immune molecules evolve among vertebrates. Here, we utilized carry out comparative transcriptome analysis in various immune cells across seven vertebrate species. Single-cell RNA sequencing (scRNA-seq). We uncovered both conserved and species-specific profiling of gene expression in innate and adaptive immunity. Macrophages exhibited highly-diversified genes and developed sophisticated molecular signaling networks along with evolution, indicating effective and versatile functions in higher species. In contrast, B cells conservatively evolved with less differentially-expressed genes in analyzed species. Interestingly, T cells represented a dominant immune cell populations in all species and unique T cell populations were identified in zebrafish and pig. We also revealed compensatory TCR cascade components utilized by different species. Inter-species comparison of core gene programs demonstrated mouse species has the highest similarity in immune transcriptomes to human. Therefore, our comparative study reveals gene transcription characteristics across multiple vertebrate species during the evolution of immune system, providing insights for species-specific immunity as well as the translation of animal studies to human physiology and disease. [ABSTRACT FROM AUTHOR]