Immunology letters最新文献

The lungs face constant environmental challenges from harmless molecules, airborne pathogens and harmful agents that can damage the tissue. The lungs’ immune system includes numerous tissue-resident lymphocytes that contribute to maintain tissue homeostasis and to the early initiation of immune responses. Amongst tissue-resident lymphocytes, Mucosal Associated Invariant T (MAIT) cells are present in human and murine lungs and emerging evidence supports their contribution to immune responses during infections, chronic inflammatory disorders and cancer. This review explores the mechanisms underpinning MAIT cell functions in the airways, their impact on lung immunity and the potential for targeting pulmonary MAIT cells in a therapeutic context.

The present study focused on the efficacy and role of triptolide (TPL) in relieving symptoms of acute gouty arthritis (AGA) in vivo and in vitro. The effects of TPL in AGA were investigated in monosodium urate (MSU)-treated rat ankles, RAW264.7 macrophages, and neutrophils isolated from mouse peritoneal cavity. Observation of pathological changes in the ankle joint of rats. Enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of inflammatory factors and chemokines. The levels of the indicators of macrophage M1/M2 polarization, and the mechanistic targets of Akt and rapamycin complex 2, were determined via western blotting and RT-qPCR. The expression levels of CD86 and CD206 were detected using immunohistochemistry. Neutrophil migration was observed via air pouch experiments in vivo and Transwell cell migration assay in vitro. Myeloperoxidase (MPO) and Neutrophil elastase (NE) release was analyzed by via immunohistochemistry and immunofluorescence. The expression levels of beclin-1, LC3B, Bax, Bcl-2, and cleaved caspase-3 in neutrophils were determined via western blotting and immunofluorescence. Neutrophil apoptosis was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Our results suggest that TPL inhibited inflammatory cell infiltration in rat ankle joints and inflammatory factor and chemokine secretion in rat serum, regulated macrophage polarization through the PI3K/AKT signaling pathway, suppressed inflammatory factor and chemokine expression in neutrophils, and inhibited neutrophil migration, neutrophil extracellular trap formation, transitional autophagy, and apoptosis. This suggests that TPL can prevent and treat MSU-induced AGA by regulating macrophage polarization through the PI3K/Akt pathway and modulating neutrophil activity.

The collaboration between the microbiota, mucosa, and intestinal epithelium is crucial for defending against pathogens and external antigens. Dysbiosis disrupts this balance, allowing pathogens to thrive and potentially enter the bloodstream, triggering immune dysregulation and potentially leading to sepsis. Antimicrobial peptides like LL-37 and CRAMP are pivotal in innate immune defense. Their expression varies with infection severity, exhibiting a dual pro- and anti-inflammatory response. Understanding this dynamic is key to comprehending sepsis progression.

In our study, we examined the inflammatory response in CRAMP knockout mice post-cecal ligation and puncture (CLP). We assessed its impact on brain tissue damage and the intestinal microbiota. Our findings revealed higher gene expression of S100A8 and S100A9 in the prefrontal cortex of wild-type mice versus CRAMP-knockout mice. This trend was consistent in the hippocampus and cerebellum, although protein concentrations remained constant. Notably, there was a notable increase in Escherichia coli, Lactobacillus spp., and Enterococcus faecalis populations in wild-type mice 24 h post-CLP compared to the CRAMP-deficient group. These results align with our previous data suggesting that the absence of CRAMP may confer protection in this sepsis model.

Thymic epithelial cells participate in the maturation and selection of T lymphocytes. This review explores recent insights from single-cell sequencing regarding classifying thymic epithelial cells in both normal and neoplastic thymus. Cortical thymic epithelial cells facilitate thymocyte differentiation and contribute to positive selection. Medullary epithelial cells are distinguished by their expression of AIRE. Cells progress from a pre-AIRE state, containing precursors with cortical and medullary characteristics, termed junctional cells. Mature medullary epithelial cells exhibit promiscuous gene expression and after that downregulate AIRE mRNA. Post-AIRE cells can adopt a Hassall corpuscle-like phenotype or exhibit distinctive differentiation characteristics including tuft cells, ionocytes, neuroendocrine cells, and myoid cells.

Objective

We focused to analyze the time-course changes at pre- and post-flare of T peripheral helper (Tph) cells and circulating T follicular helper (Tfh) cells in the blood of patients with systemic lupus erythematosus (SLE) with lupus low disease activity state (LLDAS) before flare.

Methods

This study included inactive (n = 29) and active (n = 55) patients with SLE. Tph subsets, Tfh subsets, CD11c^hi B cells, and plasma cells in the blood were determined by flow cytometry. The blood levels of cytokines including interferons (IFNs) were measured by electrochemiluminescence assay or cytokine beads array.

Results

Active SLE patients exhibited the increased frequency of Tph1, Tph2, Tfh1, and Tfh2 subsets when compared to inactive patients, but no clear changes in the other subsets. During the treatment with medications, Tph1, Tph2, and Tfh2 subsets were significantly reduced along with disease activity and Tph1 and Tph2 subsets were positively correlated with SLE disease activity index (SLEDAI). The time course analysis of patients at pre- and post-flare revealed that in the patients at LLDAS before flare, Tph subsets and Tfh subsets were relatively low levels. At the flare, Tph cells, particularly Tph1 and Tph2 subsets, were increased and correlated with SLEDAI. Furthermore, the blood levels of IFN-α2a, IFN-γ, and IFN-λ1 were low in the patients with LLDAS before flare but these IFNs, particularly IFN-λ1, were increased along with flare.

Conclusion

Increased frequency of Tph1 and Tph2 subsets and elevated levels of serum IFN-λ1 are presumably critical for triggering of flare in SLE.

Objective

To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5–11 years of age.

Methods

This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5–11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated.

Results

A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days).

Conclusion

In this study with children 5–11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference.

Trial registration number

ClinicalTrials.gov number, NCT05403307 (https://classic.clinicaltrials.gov/ct2/show/NCT05403307)

Pemphigus vulgaris (PV) is a rare autoimmune disorder where autoantibodies target the desmosomal proteins resulting in blistering of oral mucosa and skin. While the pathogenesis of PV is mainly mediated by the adaptive immune system, key players of innate immunity are also emerging. This study outlines the phenotypic as well as functional attributes of NK cells in PV. Through in-depth analysis using flow cytometry we identified an increase in the frequency of CD56⁺ CD3^- NK cells and their subtypes in periphery. Along with this there is an increased frequency of IFNγ⁺ CD56^bright CD16^dim NK cells. mRNA expression of sorted NK cells for differentially expressed genes, particularly key transcription factors such as T-bet and EOMES, as well as surface receptors like NKG2D and KIR2D, and the cytokine IFNγ, displayed significant upregulation. A significant activation of NK cells was seen in the disease state. The levels of perforin and IFNγ were significantly elevated in the culture supernatants of patients. Additionally, a significantly higher cytotoxicity of NK cells in PV was observed. In lesioned tissues of PV, NK related markers were significantly increased. Lastly, we observed NK cells using confocal microscopy in the tissue biopsies of patients which showed significant infiltration of CD56⁺ CD3^- NK cells at the lesional sites. This study aimed to shed light on the pivotal role of NK cells in the immunopathology of PV, offering a thorough understanding of their behaviour and changes in expression which might help in contributing to the development of novel therapeutics.

Melatonin is the major product both synthesized and secreted by the pineal gland during the night period and it is the principal chronobiotic hormone that regulates the circadian rhythms and seasonal changes in vertebrate biology. Moreover, melatonin shows both a broad distribution along the phylogenetically distant organisms and a high functional versatility. At the present time, a significant amount of experimental evidence has been reported in scientific literature and has clearly shown a functional relationship between the endocrine, nervous, and immune systems. The biochemistry basis of the functional communication between these systems is the utilization of a common chemicals signals. In this framework, at present melatonin is considered to be a relevant member of the so-called neuro-endocrine-immunological network. Thus, both in vivo and in vitro investigations conducted in both experimental animals and humans, have clearly documented that melatonin has an important immunomodulatory role. However, most of the published results refer to information on T lymphocytes, i.e., cell-mediated immunity. On the contrary, fewer studies have been carried out on B lymphocytes, the cells responsible for the so-called humoral immunity. In this review, we have focused on the biological role of melatonin in the humoral immunity. More precisely, we report the actions of melatonin on B lymphocytes biology and on the production of different types of antibodies.

The thymus is the organ where functional and self-tolerant T cells are selected through processes of positive and negative selection before migrating to the periphery. The antigenic peptides presented on MHC class I molecules of thymic epithelial cells (TECs) in the cortex and medulla of the thymus are key players in these processes. It has been theorized that these cells express different proteasome isoforms, which generate MHC class I immunopeptidomes with features that differentiate cortex and medulla, and hence positive and negative CD8⁺ T cell selection. This theory is largely based on mouse models and does not consider the large variety of noncanonical antigenic peptides that could be produced by proteasomes and presented on MHC class I molecules. Here, we review the multi-omics, biochemical and cellular studies carried out on mouse models and human thymi to investigate their content of proteasome isoforms, briefly summarize the implication that noncanonical antigenic peptide presentation in the thymus could have on CD8⁺ T cell repertoire and put these aspects in the larger framework of anatomical and immunological differences between these two species.

Pancreatic Ductal Adenocarcinoma (PDAC) is the most frequent pancreatic cancer and represents one of the most aggressive human neoplasms. Typically identified at advance stage disease, most PDAC tumors are unresectable and resistant to standard therapies.

The immunosuppressive microenvironment in PDAC impedes tumor control but a greater understanding of the complex stromal interactions within the tumor microenvironment (TME) and the development of strategies capable of restoring antitumor effector immune responses could be crucial to fight this aggressive tumor and its spread.

Natural Killer (NK) cells play a crucial role in cancer immunosurveillance and represent an attractive target for immunotherapies, both as cell therapy and as a pharmaceutical target.

This review describes some crucial components of the PDAC TME (collagens, soluble factors and fibroblasts) that can influence the presence, phenotype and function of NK cells in PDAC patients tumor tissue. This focused overview highlights the therapeutic relevance of dissecting the complex stromal composition to define new strategies for NK cell-based immunotherapies to improve the treatment of PDAC.