Ox40-Cre-mediated deletion of BRD4 reveals an unexpected phenotype of hair follicle stem cells in alopecia.

BRD4 is a bromodomain extraterminal domain family member and functions primarily as a chromatin reader regulating genes involved in cell-fate decisions. Here, we bred Brd4fl/fl Ox40-Cre mice in which Brd4 was conditionally deleted in OX40-expressing cells to examine the role of BRD4 in regulating immune responses. We found that the Brd4fl/fl Ox40-Cre mice developed profound alopecia and dermatitis, while other organs and tissues were not affected.

Suppression of FOXP3 expression by the AP-1 family transcription factor BATF3 requires partnering with IRF4.

FOXP3 is the lineage-defining transcription factor for Tregs, a cell type critical to immune tolerance, but the mechanisms that control FOXP3 expression in Tregs remain incompletely defined, particularly as it relates to signals downstream of TCR and CD28 signaling. Herein, we studied the role of IRF4 and BATF3, two transcription factors upregulated upon T cell activation, to the conversion of conventional CD4+ T cells to FOXP3+ T cells (iTregs) . We found that IRF4 must partner with BATF3 to bind to a regulatory region in the locus where they cooperatively repress FOXP3 expression and iTreg induction.

Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Stroke Severity and Short-Term Prognosis in Acute Ischemic Stroke With Intracranial Atherosclerotic Stenosis.

Neutrophil-to-lymphocyte ratio (NLR) is an indicator of poor prognosis in acute ischemic stroke (AIS), but associations between NLR with stroke severity and prognosis of intracranial atherosclerotic stenosis (ICAS)-related ischemic events have not been well-elucidated; therefore, we aimed to evaluate whether admission NLR levels correlate with the early stroke severity and short-term functional prognosis in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). This retrospective study enrolled 899 consecutive patients with AIS attributed to ICAS at Xiangya Hospital stroke center between May 2016 and September 2020. The initial stroke severity was rated by the admission National Institutes of Health Stroke Scale (NIHSS) scores, and the short-term prognosis was evaluated using the 14-day modified Rankin Scale (mRS) scores after stroke onset.

Molecular Biomarkers Associated with Early-Onset Symptomatic Intracranial Atherosclerosis.

Purpose: Previous studies have shown a rising incidence of early-onset symptomatic intracranial atherosclerosis (sICAS), which has brought a severe economic burden to social development. This study aimed to evaluate the molecular biomarkers associated with early-onset sICAS and to seek possible intervention strategies for early prevention.

Patients And Methods: We consecutively recruited patients with sICAS and divided them into two groups based on age: early-onset sICAS group as age ≤60 years old and late-onset sICAS group as age >60 years old.

The transcription factor RelB restrains group 2 innate lymphoid cells and type 2 immune pathology in vivo.

The exact relationships between group 2 innate lymphoid cells (ILC2s) and Th2 cells in type 2 pathology, as well as the mechanisms that restrain the responses of these cells, remain poorly defined. Here we examined the roles of ILC2s and Th2 cells in type 2 lung pathology in vivo using germline and conditional Relb-deficient mice. We found that mice with germline deletion of Relb (Relb) spontaneously developed prominent type 2 pathology in the lung, which contrasted sharply with mice with T-cell-specific Relb deletion (RelbCd4-Cre), which were healthy with no observed autoimmune pathology.

Epigenetically modifying the Foxp3 locus for generation of stable antigen-specific Tregs as cellular therapeutics.

Foxp3+ regulatory T cells (Tregs) are potent immunoregulatory cells, prompting strong interests in manipulating them for therapeutic purposes. However, significant challenges remain, including their heterogeneity and functional instability. Here we focused on the inducible Tregs (iTregs) and studied whether the Foxp3 locus can be epigenetically edited ex vivo to produce stable therapeutic iTregs.