SHIP-1 regulates the differentiation and function of Tregs via inhibiting mTORC1 activity.

Cell metabolism is crucial for orchestrating the differentiation and function of regulatory T cells (Tregs). However, the underlying mechanism that coordinates cell metabolism to regulate Treg activity is not completely understood. As a pivotal molecule in lipid metabolism, the role of SHIP-1 in Tregs remains unknown.

Senescence detection using reflected light.

Senescence is an important cellular program occurring in development, tissue repair, cancer, and aging. Increased senescence is also associated with disease states, including obesity and Type 2 diabetes (T2D). Characterizing and quantifying senescent cells at a single cell level has been challenging and particularly difficult in large primary cells, such as human adipocytes.

The roles of mathematical language and emergent literacy skills in the longitudinal prediction of specific early numeracy skills.

Mathematical language (i.e., content-specific language used in mathematics) and emergent literacy skills predict children's broad numeracy development.

Tumor-associated NK cells drive MDSC-mediated tumor immune tolerance through the IL-6/STAT3 axis.

Apart from their killer identity, natural killer (NK) cells have integral roles in shaping the tumor microenvironment. Through immune gene deconvolution, the present study revealed an interplay between NK cells and myeloid-derived suppressor cells (MDSCs) in nonresponders of immune checkpoint therapy. Given that the mechanisms governing the outcome of NK cell-to-myeloid cell interactions remain largely unknown, we sought to investigate the cross-talk between NK cells and suppressive myeloid cells.

Controlled WASp activity regulates the proliferative response for Treg cell differentiation in the thymus.

The Wiskott-Aldrich syndrome protein (WASp) regulates actin cytoskeletal dynamics and function of hematopoietic cells. Mutations in the WAS gene lead to two different syndromes; Wiskott-Aldrich syndrome (WAS) caused by loss-of-function mutations, and X-linked neutropenia (XLN) caused by gain-of-function mutations. We previously showed that WASp-deficient mice have a decreased number of regulatory T (Treg) cells in the thymus and the periphery.

Natural killer cells drive 4-1BBL positive uveal melanoma towards EMT and metastatic disease.

Background: Inflammation in the eye is often associated with aggravated ocular diseases such as uveal melanoma (UM). Poor prognosis of UM is generally associated with high potential of metastatic liver dissemination. A strong driver of metastatic dissemination is the activation of the epithelial-mesenchymal transition (EMT) regulating transcription factor ZEB1, and high expression of ZEB1 is associated with aggressiveness of UM.

Exposure of volunteers to microgravity by dry immersion bed over 21 days results in gene expression changes and adaptation of T cells.

The next steps of deep space exploration are manned missions to Moon and Mars. For safe space missions for crew members, it is important to understand the impact of space flight on the immune system. We studied the effects of 21 days dry immersion (DI) exposure on the transcriptomes of T cells isolated from blood samples of eight healthy volunteers.

Next generation of astronauts or ESA astronaut 2.0 concept and spotlight on immunity.

Although we have sent humans into space for more than 50 years, crucial questions regarding immune response in space conditions remain unanswered. There are many complex interactions between the immune system and other physiological systems in the human body. This makes it difficult to study the combined long-term effects of space stressors such as radiation and microgravity.

Establishment and characterization of a novel breast implant-associated anaplastic large cell lymphoma cell line and PDX model (BIA-XR1) with a unique KRAS mutation.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon T-cell lymphoma type with distinct clinical, molecular and genetic features. Establishment of BIA-ALCL cell lines and patient-derived xenograft (PDX) models are essential experimental tools to investigate the molecular pathogenesis of the disease. We characterized a novel BIA-ALCL cell line and PDX model, named BIA-XR1, derived from a patient with textured breast implant who developed lymphoma.

Understanding immunoactinopathies: A decade of research on WAS gene defects.

Immunoactinopathies caused by mutations in actin-related proteins are a growing group of inborn errors of immunity (IEI). Immunoactinopathies are caused by a dysregulated actin cytoskeleton and affect hematopoietic cells especially because of their unique capacity to survey the body for invading pathogens and altered self, such as cancer cells. These cell motility and cell-to-cell interaction properties depend on the dynamic nature of the actin cytoskeleton.

SHP-1 localization to the activating immune synapse promotes NK cell tolerance in MHC class I deficiency.

Natural killer (NK) cells recognize virally infected cells and tumors. NK cell function depends on balanced signaling from activating receptors, recognizing products from tumors or viruses, and inhibitory receptors (such as KIR/Ly49), which recognize major histocompatibility complex class I (MHC-I) molecules. KIR/Ly49 signaling preserves tolerance to self but also conveys reactivity toward MHC-I-low target cells in a process known as NK cell education.

Increased cross-presentation by dendritic cells and enhanced anti-tumour therapy using the Arp2/3 inhibitor CK666.

Background: Dendritic cell (DC) vaccines for cancer therapy offer the possibility to let the patient's own immune system kill cancer cells. However, DC vaccines have shown less efficacy than expected due to failure to induce cancer cell killing and by activating T regulatory cells.

Methods: We tested if inhibition of signalling via WASp and Arp2/3 using the small molecule CK666 would enhance DC-mediated killing of tumour cells in vitro and in vivo.

T cell responses at diagnosis of amyotrophic lateral sclerosis predict disease progression.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, involving neuroinflammation and T cell infiltration in the central nervous system. However, the contribution of T cell responses to the pathology of the disease is not fully understood. Here we show, by flow cytometric analysis of blood and cerebrospinal fluid (CSF) samples of a cohort of 89 newly diagnosed ALS patients in Stockholm, Sweden, that T cell phenotypes at the time of diagnosis are good predictors of disease outcome.

Mutant p53 gain of function mediates cancer immune escape that is counteracted by APR-246.

Background: p53 mutants contribute to the chronic inflammatory tumour microenvironment (TME). In this study, we address the mechanism of how p53 mutants lead to chronic inflammation in tumours and how to transform it to restore cancer immune surveillance.

Methods: Our analysis of RNA-seq data from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) project revealed that mutant p53 (mtp53) cancers correlated with chronic inflammation.

Involvement of MST1/mTORC1/STAT1 activity in the regulation of B-cell receptor signalling by chemokine receptor 2.

Background: CCR2 is involved in maintaining immune homeostasis and regulating immune function. This study aims to elucidate the mechanism by which CCR2 regulates B-cell signalling.

Methods: In Ccr2-knockout mice, the development and differentiation of B cells, BCR proximal signals, actin movement and B-cell immune response were determined.

Home science interactions and their relation to children's science core knowledge in preschool.

A limited body of work has examined the nature and scope of young children's science-related activities outside of the school context, and thus there is little understanding or consensus regarding what comprises the home science environment (HSE; e.g., interactions, activities, resources) and how specific factors of the HSE relate to children's science performance.

FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors.

The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant to expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage.

A gain-of-function variant in the Wiskott-Aldrich syndrome gene is associated with a MYH9-related disease-like syndrome.

While loss-of-function variants in the WAS gene are associated with Wiskott-Aldrich syndrome and lead to microthrombocytopenia, gain-of-function variants of WAS are associated with X-linked neutropenia (XLN) and the absence of microthrombocytopenia. Only a few XLN families have been reported so far, and their platelet phenotype was not described in detail. To date, no renal involvement was described in XLN.

SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism.

The SARS-CoV-2 infection causes severe immune disruption. However, it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients. In our study, we have characterized the immune phenotype of B cells from 15 recovered COVID-19 patients, and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation, but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation.

Immune Dysregulation in IgG-Related Disease.

Immunoglobin G-related disease (IgG-RD) is one of the newly discovered autoimmune diseases characterized by elevated serum IgG concentrations and multi-organ fibrosis. Despite considerable research and recent advances in the identification of underlying immunological processes, the etiology of this disease is still not clear. Adaptive immune cells, including different types of T and B cells, and cytokines secreted by these cells play a vital role in the pathogenesis of IgG-RD.

Signaling networks in B cell development and related therapeutic strategies.

B cells are essential for Ab production during humoral immune responses. From decades of B cell research, there is now a detailed understanding of B cell subsets, development, functions, and most importantly, signaling pathways. The complicated pathways in B cells and their interactions with each other are stage-dependent, varying with surface marker expression during B cell development.

Novel Discoveries in Immune Dysregulation in Inborn Errors of Immunity.

With the expansion of our knowledge on inborn errors of immunity (IEI), it gradually becomes clear that immune dysregulation plays an important part. In some cases, autoimmunity, hyperinflammation and lymphoproliferation are far more serious than infections. Thus, immune dysregulation has become significant in disease monitoring and treatment.

The WASp L272P gain-of-function mutation alters dendritic cell coordination of actin dynamics for migration and adhesion.

Dendritic cells (DCs) devoid of the actin regulator Wiskott-Aldrich syndrome protein (WASp) show reduced directed migration and decreased formation of podosome adhesion structures. We examined DCs expressing a gain-of-function mutation in WASp, WASp L272P, identified in X-linked neutropenia patients. Analysis of WASp L272P DCs was compared to WASp-deficient DCs to examine how WASp activity influences DC migratory responses.