Paroxetine attenuates sepsis by preserving the expression of the G protein-coupled chemokine receptor CXCR2 on neutrophils.

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is associated with impaired neutrophil migration to the infectious focus owing to G protein-coupled receptor kinase (GRK2)-dependent CXCR2 internalization. In the present study, we investigated whether paroxetine, an antidepressant that belongs to the selective serotonin reuptake inhibitor (SSRI) class of drugs and that is also identified as a GRK2 inhibitor, can improve neutrophil recruitment in the cecal ligation and puncture (CLP)-induced sepsis model. Moderate (mCLP) and severe (sCLP) polymicrobial peritonitis were induced in C57BL/6 mice.

Second Edition of the Scientists of Tomorrow/Cientistas do Amanhã Project: advancing scientific thinking, methodology, and equitable education.

Ensuring quality education, providing vocational training, and promoting communication technology, technical, and scientific programs are goals set by the United Nations to enhance learning opportunities for all. Critical thinking, fostered through theoretical and practical activities, is essential for building relevant skills, including literacy and numeracy. The Scientists of Tomorrow/Cientistas do Amanhã project is a reproducible initiative that can be implemented in other research centers and schools.

Schizophrenia-associated complement component C4 induces maturation and reactivity in human astrocytes.

Beyond its canonical role in innate immunity, the complement system (CS) has been increasingly implicated in brain development and disease. Elevated expression of complement component C4, in particular, is strongly associated with an increased risk of schizophrenia (SCZ), potentially by promoting excessive synaptic pruning. Astrocytes, the primary producers of CS components in the brain and expressers of multiple CS receptors, play crucial roles in synaptic formation and refinement.

Innate lymphoid cells in bone marrow and peripheral blood of healthy individuals and in bone marrow of patients with myelodysplastic syndromes.

Introduction: Innate lymphoid cells (ILCs) are a recently characterized subset of lymphocytes with critical effector and regulatory functions. Based on distinct phenotypic markers and cytokine secretion profiles, ILCs are classified into three subtypes: ILC1, ILC2, and ILC3. The bone marrow (BM) microenvironment in myelodysplastic neoplasms (MDS) is characterized by heightened cytokine levels and dysregulated inflammatory responses, potentially affecting immune cell composition.

CXCR4 PD-L1 neutrophils are increased in non-survived septic mice.

The dysregulated host response to infections can lead to sepsis, a complex disease characterized by a spectrum of clinical phenotypes. Using scRNA-seq, we analyzed the immune cell of survived and non-survived CLP-septic mice to gain insights into the immunological mechanisms by which neutrophils contribute to the hyperinflammatory phenotype. Our findings reveal that non-survived mice exhibit increased frequencies of immature CXCR4 PD-L1 neutrophils in the bloodstream, accompanied by an accumulation of trafficking-specific CXCR4 PD-L1 neutrophils into the lungs.

AIM2 promotes T17 cells differentiation by regulating RORγt transcription activity.

AIM2 is an interferon-inducible HIN-200 protein family member and is well-documented for its roles in innate immune responses as a DNA sensor. Recent studies have highlighted AIM2's function on regulatory T cells (Treg) and follicular T cells (Tfh). However, its involvement in Th17 cell differentiation remains unclear.

Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons.

Interleukin (IL)-17a has been highly conserved during evolution of the vertebrate immune system and widely studied in contexts of infection and autoimmunity. Studies suggest that IL-17a promotes behavioral changes in experimental models of autism and aggregation behavior in worms. Here, through a cellular and molecular characterization of meningeal γδ17 T cells, we defined the nearest central nervous system-associated source of IL-17a under homeostasis.

TGF-β1 functional polymorphisms: a review.

Transforming Growth Factor β (TGF-β) is a multifunctional cytokine that plays a role in several biological processes. TGF-β1 is the most abundantly expressed isoform, associated with susceptibility to various diseases, and several polymorphisms have been described in the TGF-β1 gene structure, and some of them have been associated with functional implications. To date, eight single-nucleotide polymorphisms (SNPs) and one deletion/insertion polymorphism have been shown to affect TGF-β1 expression (rs2317130, rs11466313, rs1800468, rs1800469, rs11466314, rs1800471, rs1800470, and rs11466316); some of these interfere with transcriptional regulation by affecting the binding of transcription factors binding, while others interfere with protein production.