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Mesenchymal stem cells offer a drug-tolerant and immune-privileged niche to Mycobacterium tuberculosis.

Anti-tuberculosis (TB) drugs, while being highly potent in vitro, require prolonged treatment to control Mycobacterium tuberculosis (Mtb) infections in vivo. We report here that mesenchymal stem cells (MSCs) shelter Mtb to help tolerate anti-TB drugs. MSCs readily take up Mtb and allow unabated mycobacterial growth despite having a functional innate pathway of phagosome maturation. Unlike macrophage-resident ones, MSC-resident Mtb tolerates anti-TB drugs remarkably well, a phenomenon requiring proteins ABCC1, ABCG2 and vacuolar-type H+ATPases. Additionally, the classic pro-inflammatory cytokin

Tolerance May Be More Appropriate Than Immunity When Describing Chronic Malaria Infections.

Adults who have not grown up in a malaria-endemic area may experience severe malaria soon after entering a malarious area. Such mortality is usually limited to a short period of time (months), after which they are thought to be "immune." Such anti-disease immunity may be more accurately considered as tolerance. Malaria rates of British soldiers during the Second World War reflected their time with suppressed infections and the transmission levels. Black workers from non-endemic areas on the Panama Canal experienced higher initial mortality and infection rates than co-located white workers for

Human interleukin-2 receptor β mutations associated with defects in immunity and peripheral tolerance.

Interleukin-2, which conveys essential signals for immunity, operates through a heterotrimeric receptor. Here we identify human interleukin-2 receptor (IL-2R) β chain (IL2RB) gene defects as a cause of life-threatening immune dysregulation. We report three homozygous mutations in the IL2RB gene of eight individuals from four consanguineous families that cause disease by distinct mechanisms. Nearly all patients presented with autoantibodies, hypergammaglobulinemia, bowel inflammation, dermatological abnormalities, lymphadenopathy, and cytomegalovirus disease. Patient T lymphocytes lacked surfac

T cell-dendritic cell interaction dynamics during the induction of respiratory tolerance and immunity.

Dendritic cells (DCs) residing in the lung are known to acquire inhaled Ag and, after migration to the draining bronchial lymph node (brLN), to present it to naive T cells in an either tolerogenic or immunogenic context. To visualize endogenous lung-derived DCs, we applied fluorescent latex beads (LXs) intratracheally, thereby in vivo labeling the majority of phagocytic cells within the lung. Of note, LX-bearing cells subsequently arriving in the draining brLN were found to represent lung-derived migratory DCs. Imaging explanted brLN by two-photon laser-scanning microscopy, we quantitatively a

Tolerance and immunity following in utero transplantation of allogeneic fetal liver cells: the cytokine shift.

Although in utero transplantation (IUT) has resulted in donor-specific tolerance to posnatal solid organ transplantation, the mechanisms of this tolerance remain poorly understood. Our recent findings demonstrate that under specific conditions prenatal injection of allogeneic cells may lead to allosensitization instead of tolerance. These laboratory observations were supported by clinical findings as well, and therefore suggested that, depending on the conditions of prenatal transplantation, tolerance or immunity may develop. The present study explored the role of CD4 cells, cytokines, and I-E

Correlative Monitoring of Immune Activation and Tissue Damage in Malignant Melanoma-An Algorithm for Identification of Tolerance Breakage During Immune Checkpoint Inhibitor Therapy of Cancer.

We describe an innovative approach for identification of tolerance breakage during immune checkpoint inhibitor therapy in malignant melanoma. Checkpoint inhibitor therapy enhances the immunologic clearance of cancer by suppressing pathways which induce immune suppression and tolerance. We posit that by analyzing temporal correlations of key markers of immune activation and tissue damage it would be possible to detect the onset of anticancer immune reaction as well as of immunologic adverse effects which might become crucial for optimization as well as safety of immune checkpoint inhibitor trea

Integrative multi-omics, network pharmacology, and molecular simulation of herbal compounds targeting immune tolerance mechanisms in food allergy.

Food allergies (FAs) significantly impact quality of life. Allergen-specific immunotherapy (AIT) shows promise but faces limitations such as prolonged treatment duration, systemic side effects, and poor compliance, especially in pediatric and elderly populations. Complementary and alternative medicine (CAM) may enhance AIT efficacy and safety, yet the mechanisms underlying immune tolerance remain poorly understood. This study employed an integrated in silico approach combining network pharmacology, molecular simulation, and metabolomics to investigate anti-allergic Jamu medicinal plants in FA.…

Vitamin D in Gut and Systemic Immune Tolerance and in Infections' Risk: An International Evidence-Based Consensus Statement.

Vitamin D, classically linked to calcium-phosphate metabolism and skeletal health, is increasingly recognized as a pleiotropic hormone with … ociated with alterations in gut microbiota composition, increased intestinal permeability, impaired immune tolerance, and increased susceptibility to infections and autoimmune conditions, evidence from interventional studies remains more variable. Clinical outcomes are influenced by baseline 25(OH)D status, supplementation dose and formulation, timing of intervent …

Integrated transcriptome study reveals a stress response state CD4 +T cells related to immune tolerance in breast cancer.

BACKGROUND: Lymph node status is of great clinical importance in tumor staging and prognosis where antitumoral immunity is generated and pre … e breast cancer. CONCLUSIONS: In summary, we identify a specific cluster of CD4 +T cells related to immune tolerance that serves as a new predictor for immunotherapy in breast cancer.

Insights into regulatory T-cell and type-I interferon roles in determining abacavir-induced hypersensitivity or immune tolerance.

INTRODUCTION: Clinical use of several small molecule drugs may lead to severe T-cell-mediated idiosyncratic drug hypersensitivity reactions (iDHR) linked to HLA alleles, including abacavir (ABC) with HLA-B*57:01. Due to study limitations in humans, pathogenic networks in iDHR remain elusive. HLA transgenic murine models have been proposed to bridge knowledge gaps in tolerance and susceptibility to drugs. METHODS: Mice expressing HLA-B*57:01 and Foxp3-DTR/EGFP were generated to selectively deplete regulatory T-cells (Treg) with diphtheria toxin. ABC was administered for 8 days alone or togethe

Наномедицина, направленная на ось PD-1/PD-L1 в аутоиммунных болезнях: преодоление традиционных барьеров для восстановления иммунной терпимости.

Аутоиммунные заболевания (АД) возникают в результате нарушения самодостаточности, что приводит к патогенной иммунной реакции на здоровые ткани. Иммунный контрольно-пропускной пункт PD-1/PD-L1 имеет ключевое значение для поддержания периферической терпимости путем подавления автоматически реактивных Т клеток, а его дисфункция стимулирует патогенез ревматоидного артрита (RA), системного волчанка эриматоса (SLE), множественного склероза (MS) и других AD. Обычные подходы, включая моноколональные антитела, растворимые белки с синтезом PD-L1, небольшие молекулярные или РНК-регуляторы и клеточные или

Совпадение в аннотации оригинала
Autoimmune diseases (ADs) arise from the breakdown of self-tolerance, leading to pathogenic immune responses against healthy tissues. The PD … outlines a roadmap for next-generation, precision-engineered interventions aimed at reestablishing immune tolerance and improving clinical outcomes in ADs.

Sugar and arginine facilitate oral tolerance by ensuring the functionality of tolerogenic immune cell subsets in the intestine.

Although oral tolerance is a critical system in regulating allergic disorders, the mechanisms by which dietary factors regulate the induction and maintenance of oral tolerance remain unclear. To address this, we explored the differentiation and function of various immune cells in the intestinal immune system under fasting and ad libitum-fed conditions before oral ovalbumin (OVA) administration. Fasting mitigated OVA-specific Treg expansion, which is essential for oral tolerance induction. This abnormality mainly resulted from functional defects in the CX3CR1+ cells responsible for the uptake o

Shoutai Wan treatment upregulates the expression of TNFAIP3 and improves T cell immune tolerance at maternal-fetal interface.

Shoutai Wan (STW) is a traditional Chinese medicine formula used to treat various conditions. The objective of this study was to evaluate th … al-fetal interface. These molecular changes may contribute to the regulation of T cell immunity and immune tolerance during pregnancy.

Biosafety Evaluation of a Chimeric Adenoviral Vector in Mini-Pigs: Insights into Immune Tolerance and Gene Therapy Potential.

BACKGROUND: The biosafety of gene therapy products remains a major challenge to their introduction into the clinic. In particular, the probl … els in the blood of experimental animals is also consistent with the in vitro data and confirms the immune tolerance of mini-pigs to Ad5/35F-GFP. CONCLUSIONS: Here, we show the safety of Ad5/35F in a mini-pig model and provide evidence that Ad5/35F is a promising vector for gene therapy. These results advance our understanding of vector-host interactions and offe …

Immunosuppressive Polymeric Nanoparticles Targeting Dendritic Cells Alleviate Lupus Disease in Fcgr2b-/- Mice by Mediating Antigen-Specific Immune Tolerance.

Dendritic cells (DCs) are the most potent antigen-presenting cells that have multifaceted functions in the control of immune activation and tolerance. Hyperresponsiveness and altered tolerogenicity of DCs contribute to the development and pathogenesis of system lupus erythematosus (SLE); therefore, DC-targeted therapies aimed at inducing specific immune tolerance have become of great importance for the treatment of SLE. This study developed a new nanoparticle (NP) containing a biodegradable PDMAEMA-PLGA copolymer for target-oriented delivery to DCs in situ. PDMAEMA-PLGA NPs provided sustained …