Efficient gene deletion of Integrin alpha 4 in primary mouse CD4 T cells using CRISPR RNA pair-mediated fragmentation.

The functional specialization of CD4 T lymphocytes into various subtypes, including T1 and T cells, is crucial for effective immune responses. T cells facilitate B cell differentiation within germinal centers, while T1 cells are vital for cell-mediated immunity against intracellular pathogens. Integrin α4, a cell surface adhesion molecule, plays significant roles in cell migration and co-stimulatory signaling.

Transcriptional and methylation outcomes of didehydro-cortistatin A use in HIV-1-infected CD4 T cells.

Ongoing viral transcription from the reservoir of HIV-1 infected long-lived memory CD4 T cells presents a barrier to cure and associates with poorer health outcomes for people living with HIV, including chronic immune activation and inflammation. We previously reported that didehydro-cortistatin A (dCA), an HIV-1 Tat inhibitor, blocks HIV-1 transcription. Here, we examine the impact of dCA on host immune CD4 T-cell transcriptional and epigenetic states.

Nuances in the interpretation and utility of donor-derived cell-free DNA in lung transplantation following allogeneic hematopoietic stem cell transplantation - Case report.

Respiratory complications following allogeneic HSCT can lead to severe morbidity and mortality. Lung transplantation (LT) is a potential treatment for select patients with late-onset non-infectious pulmonary complications post-HSCT. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for monitoring the health of allografts following LT.

Experimentally elevated corticosterone does not affect bacteria killing ability of breeding female tree swallows (Tachycineta bicolor).

The immune system can be modulated when organisms are exposed to acute or chronic stressors. Glucocorticoids (GCs), the primary hormonal mediators of the physiological stress response, are suspected to play a crucial role in immune modulation. However, most evidence of stress-associated immunomodulation does not separate the effects of glucocorticoid-dependent pathways from those of glucocorticoid-independent mechanisms on immune function.

solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during lung perfusion of FOLFOX.

In vivo lung perfusion (IVLP) is a novel isolated lung technique developed to enable the local, in situ administration of high-dose chemotherapy to treat metastatic lung cancer. Combination therapy using folinic acid (FOL), 5-fluorouracil (F), and oxaliplatin (OX) (FOLFOX) is routinely employed to treat several types of solid tumours in various tissues. However, F is characterized by large interpatient variability with respect to plasma concentration, which necessitates close monitoring during treatments using of this compound.

Spatiotemporal resolution of germinal center Tfh cell differentiation and divergence from central memory CD4 T cell fate.

Follicular helper T (Tfh) cells are essential for germinal center (GC) B cell responses. However, it is not clear which PD-1CXCR5Bcl6CD4 T cells will differentiate into PD-1CXCR5Bcl6 GC-Tfh cells and how GC-Tfh cell differentiation is regulated. Here, we report that the sustained Tigit expression in PD-1CXCR5CD4 T cells marks the precursor Tfh (pre-Tfh) to GC-Tfh transition, whereas TigitPD-1CXCR5CD4 T cells upregulate IL-7Rα to become CXCR5CD4 T memory cells with or without CCR7.

Transcriptional programming of CD4 T differentiation in viral infection balances effector- and memory-associated gene expression.

After resolution of infection, T cells differentiate into long-lived memory cells that recirculate through secondary lymphoid organs or establish residence in tissues. In contrast to CD8 tissue-resident memory T cells (T), the developmental origins and transcriptional regulation of CD4 T remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profiles of CD4 T in the small intestine (SI) responding to acute viral infection, revealing a shared gene expression program and chromatin accessibility profile with circulating T1 and the progressive acquisition of a mature T program.

Acute transcutaneous electrical stimulation (TES) augments esophageal contractility in patients with weak peristalsis.

Background: Lung transplantation (LTx) remains controversial in patients with absent peristalsis (AP) given the increased risk for gastroesophageal reflux (GER), and chronic lung allograft dysfunction. Furthermore, specific treatments to facilitate LTx in those with AP have not been widely described. Transcutaneous Electrical Stimulation (TES) has been reported to improve foregut contractility in LTx patients and therefore we hypothesize that TES may augment the esophageal motility of patients with ineffective esophageal motility (IEM).

Mll1 pioneers histone H3K4me3 deposition and promotes formation of CD8 T stem cell memory.

CD8 T cells with stem cell-like properties (T ) sustain adaptive immunity to intracellular pathogens and tumors. However, the developmental origins and chromatin regulatory factors (CRFs) that establish their differentiation are unclear. Using an RNA interference screen of all CRFs we discovered the histone methylase Mll1 was required during T cell receptor (TCR) stimulation for development of a T precursor state and mature memory (T ) cells, but not short-lived or transitory effector cell-like states, in response to viral infections and tumors.

The Chromatin Regulator Mll1 Supports T Follicular Helper Cell Differentiation by Controlling Expression of Bcl6, LEF-1, and TCF-1.

T follicular helper (TFH) cells are essential for developing protective Ab responses following vaccination. Greater understanding of the genetic program leading to TFH differentiation is needed. Chromatin modifications are central in the control of gene expression.

DNA architectural protein CTCF facilitates subset-specific chromatin interactions to limit the formation of memory CD8 T cells.

Although the importance of genome organization for transcriptional regulation of cell-fate decisions and function is clear, the changes in chromatin architecture and how these impact effector and memory CD8 T cell differentiation remain unknown. Using Hi-C, we studied how genome configuration is integrated with CD8 T cell differentiation during infection and investigated the role of CTCF, a key chromatin remodeler, in modulating CD8 T cell fates through CTCF knockdown approaches and perturbation of specific CTCF-binding sites. We observed subset-specific changes in chromatin organization and CTCF binding and revealed that weak-affinity CTCF binding promotes terminal differentiation of CD8 T cells through the regulation of transcriptional programs.

The chaperone protein p32 stabilizes HIV-1 Tat and strengthens the p-TEFb/RNAPII/TAR complex promoting HIV transcription elongation.

HIV gene expression is modulated by the combinatorial activity of the HIV transcriptional activator, Tat, host transcription factors, and chromatin remodeling complexes. To identify host factors regulating HIV transcription, we used specific single-guide RNAs and endonuclease-deficient Cas9 to perform chromatin affinity purification of the integrated HIV promoter followed by mass spectrometry. The scaffold protein, p32, also called ASF/SF2 splicing factor-associated protein, was identified among the top enriched factors present in actively transcribing HIV promoters but absent in silenced ones.

A prospective examination of swallow and cough dysfunction after lung transplantation.

Objectives: Swallow and cough dysfunction are possible surgical complications of lung transplantation (LT). We examined voluntary cough strength, sensorimotor reflexive cough integrity, and swallow-related respiratory rate (RR) across swallowing safety and aspiration response groups in recovering LT recipients.

Methods: Forty-five LT recipients underwent flexible endoscopic evaluation of swallowing indexed by the validated Penetration Aspiration Scale.

The Transcription Factor YY-1 Is an Essential Regulator of T Follicular Helper Cell Differentiation.

T follicular helper (T) cells are a specialized subset of CD4 T cells that deliver critical help signals to B cells for the production of high-affinity Abs. Understanding the genetic program regulating T differentiation is critical if one wants to manipulate T cells during vaccination. A large number of transcription factor (TFs) involved in the regulation of T differentiation have been characterized.

Corrigendum: Hyperammonemia After Lung Transplantation: Systematic Review and a Mini Case Series.

[This corrects the article DOI: 10.3389/ti.2022.

Incidence, risk factors, and sequelae of dysphagia mediated aspiration following lung transplantation.

Background: We aimed to determine dysphagia profiles before and after lung transplantation (prevalence, incidence) and to examine predictors and health-related outcomes of aspiration in individuals undergoing lung transplantation.

Methods: A retrospective single-center study of consecutive adults undergoing lung transplantation and completing a postoperative videofluoroscopic swallowing study between 2017 and 2020 was conducted. The validated penetration aspiration scale indexed swallowing safety and clinical outcomes were extracted from electronic medical records.

Hyperammonemia After Lung Transplantation: Systematic Review and a Mini Case Series.

Hyperammonemia after lung transplantation (HALT) is a rare but serious complication with high mortality. This systematic review delineates possible etiologies of HALT and highlights successful strategies used to manage this fatal complication. Seven biomedical databases and grey literature sources were searched using keywords relevant to hyperammonemia and lung transplantation for publications between 1995 and 2020.

RAVAL trial: Protocol of an international, multi-centered, blinded, randomized controlled trial comparing robotic-assisted versus video-assisted lobectomy for early-stage lung cancer.

Background: Retrospective data demonstrates that robotic-assisted thoracoscopic surgery provides many benefits, such as decreased postoperative pain, lower mortality, shorter length of stay, shorter chest tube duration, and reductions in the incidence of common postoperative pulmonary complications, when compared to video-assisted thoracoscopic surgery. Despite the potential benefits of robotic surgery, there are two major barriers against its widespread adoption in thoracic surgery: lack of high-quality prospective data, and the perceived higher cost of it. Therefore, in the face of these barriers, a prospective randomized controlled trial comparing robotic- to video-assisted thoracoscopic surgery is needed.

In vivo reprogramming of pathogenic lung TNFR2 cDC2s by IFNβ inhibits HDM-induced asthma.

Asthma is a common inflammatory lung disease with no known cure. Previously, we uncovered a lung TNFR2 conventional DC2 subset (cDC2s) that induces regulatory T cells (T) maintaining lung tolerance at steady state but promotes T2 response during house dust mite (HDM)-induced asthma. Lung IFNβ is essential for TNFR2 cDC2s-mediated lung tolerance.

Lung transplantation for acute exacerbation of interstitial lung disease.

Background: Acute exacerbations of interstitial lung diseases (AE-ILD) have a high mortality rate with no effective medical therapies. Lung transplantation is a potentially life-saving option for patients with AE-ILD, but its role is not well established. The aim of this study is to determine if this therapy during AE-ILD significantly affects post-transplant outcomes in comparison to those transplanted with stable disease.

Transcriptional Control of Cell Fate Determination in Antigen-Experienced CD8 T Cells.

Robust immunity to intracellular infections is mediated by antigen-specific naive CD8 T cells that become activated and differentiate into phenotypically and functionally diverse subsets of effector cells, some of which terminally differentiate and others that give rise to memory cells that provide long-lived protection. This developmental system is an outstanding model with which to elucidate how regulation of chromatin structure and transcriptional control establish gene expression programs that govern cell fate determination, insights from which are likely to be useful for informing the design of immunotherapeutic approaches to engineer durable immunity to infections and tumors. A unifying framework that describes how naive CD8 T cells develop into memory cells is still outstanding.

Bromodomain protein BRD4 directs and sustains CD8 T cell differentiation during infection.

In response to infection, pathogen-specific CD8 T cells differentiate into functionally diverse effector and memory T cell populations critical for resolving disease and providing durable immunity. Through small-molecule inhibition, RNAi studies, and induced genetic deletion, we reveal an essential role for the chromatin modifier and BET family member BRD4 in supporting the differentiation and maintenance of terminally fated effector CD8 T cells during infection. BRD4 bound diverse regulatory regions critical to effector T cell differentiation and controlled transcriptional activity of terminal effector-specific super-enhancers in vivo.

Kdm6b Regulates the Generation of Effector CD8 T Cells by Inducing Chromatin Accessibility in Effector-Associated Genes.

The transcriptional and epigenetic regulation of CD8 T cell differentiation is critical for balancing pathogen eradication and long-term immunity by effector and memory CTLs, respectively. In this study, we demonstrate that the lysine demethylase 6b (Kdm6b) is essential for the proper generation and function of effector CD8 T cells during acute infection and tumor eradication. We found that cells lacking Kdm6b (by either T cell-specific knockout mice or knockdown using short hairpin RNA strategies) show an enhanced generation of memory precursor and early effector cells upon acute viral infection in a cell-intrinsic manner.