Bhlhe40 Promotes CD4+ T Helper 1 Cell and Suppresses T Follicular Helper Cell Differentiation during Viral Infection.

In response to acute infection, naive CD4+ T cells primarily differentiate into T helper 1 (Th1) or T follicular helper (Tfh) cells that play critical roles in orchestrating cellular or humoral arms of immunity, respectively. However, despite the well established role of T-bet and BCL-6 in driving Th1 and Tfh cell lineage commitment, respectively, whether additional transcriptional circuits also underlie the fate bifurcation of Th1 and Tfh cell subsets is not fully understood. In this article, we study how the transcriptional regulator Bhlhe40 dictates the Th1/Tfh differentiation axis in mice.

A spatial sequencing atlas of age-induced changes in the lung during influenza infection.

Influenza virus infection causes increased morbidity and mortality in the elderly. Aging impairs the immune response to influenza, both intrinsically and because of altered interactions with endothelial and pulmonary epithelial cells. To characterize these changes, we performed single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and bulk RNA sequencing (bulk RNA-seq) on lung tissue from young and aged female mice at days 0, 3, and 9 post-influenza infection.

BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology.

Regulatory T (Treg) cells are inevitable to prevent deleterious immune responses to self and commensal microorganisms. Treg function requires continuous expression of the transcription factor (TF) FOXP3 and is divided into two major subsets: resting (rTregs) and activated (aTregs). Continuous T cell receptor (TCR) signaling plays a vital role in the differentiation of aTregs from their resting state, and in their immune homeostasis.

Loss of PBAF promotes expansion and effector differentiation of CD8 T cells during chronic viral infection and cancer.

During chronic viral infection and cancer, it has been established that a subset of progenitor CD8 T cells continuously gives rise to terminally exhausted cells and cytotoxic effector cells. Although multiple transcriptional programs governing the bifurcated differentiation trajectories have been previously studied, little is known about the chromatin structure changes regulating CD8 T cell-fate decision. In this study, we demonstrate that the chromatin remodeling complex PBAF restrains expansion and promotes exhaustion of CD8 T cells during chronic viral infection and cancer.

Lymphocytic Choriomeningitis Virus Clone 13 Infection Results in CD8 T Cell-Mediated Host Mortality in Diacylglycerol Kinase α-Deficient Mice.

Diacylglycerol is a potent element of intracellular secondary signaling cascades whose production is enhanced by cell-surface receptor agonism and function is regulated by enzymatic degradation by diacylglycerol kinases (DGKs). In T cells, stringent regulation of the activity of this second messenger maintains an appropriate balance between effector function and anergy. In this article, we demonstrate that DGKα is an indispensable regulator of TCR-mediated activation of CD8 T cells in lymphocytic choriomeningitis virus Clone 13 viral infection.

E2A-regulated epigenetic landscape promotes memory CD8 T cell differentiation.

During an acute viral infection, CD8 T cells encounter a myriad of antigenic and inflammatory signals of variable strength, which sets off individual T cells on their own differentiation trajectories. However, the developmental path for each of these cells will ultimately lead to one of only two potential outcomes after clearance of the infection-death or survival and development into memory CD8 T cells. How this cell fate decision is made remains incompletely understood.

Harnessing the IL-21-BATF Pathway in the CD8 T Cell Anti-Tumor Response.

In cancer, CD8 T cells enter a dysfunctional state which prevents them from effectively targeting and killing tumor cells. Tumor-infiltrating CD8 T cells consist of a heterogeneous population of memory-like progenitor, effector, and terminally exhausted cells that exhibit differing functional and self-renewal capacities. Our recently published work has shown that interleukin (IL)-21-producing CD4 T cells help to generate effector CD8 T cells within the tumor, which results in enhanced tumor control.

Upfront Therapies and Downstream Effects: Navigating Late Effects in Childhood Cancer Survivors in the Current Era.

Purpose Of Review: As survival rates of those diagnosed with childhood cancer improve over time, the number of long-term survivors continues to grow. Advances have not only been made in the upfront treatment of childhood cancer, but also in the identification and treatment of late complications that may arise as a result of the chemotherapy, radiotherapy, or surgical interventions required to provide a cure.

Recent Findings: As new therapies emerge that are often more targeted to cancerous cells while sparing healthy tissues, the hope is that cure can be achieved without the same long-term side effects for survivors.

Impact of Graft-Recipient ABO Compatibility on Outcomes after Umbilical Cord Blood Transplant for Nonmalignant Disease.

Existing literature shows mixed conclusions regarding the impact of ABO incompatibility on outcomes after hematopoietic stem cell transplantation. Because the future for umbilical cord blood (UCB) expansion technologies is bright, we assessed whether this typically overlooked graft characteristic impacted various outcomes after UCB transplantation (UCBT) for nonmalignant disorders (NMDs). A prospectively maintained institutional blood and marrow transplant program database was queried for all patients undergoing first UCBT for NMDs.

Restrictive Diet Control as a Means of Child Abuse.

We have recently encountered a series of cases where an obese caretaker is juxtaposed to a severely starved, malnourished dependent. The cases described all share a common characteristic: that the primary perpetrator was an obese caretaker who tried to exert absolute control over their victim's daily life in a way that included either a severe restriction or complete denial of food. Because the pathophysiology of both child abuse and obesity are incredibly complex and multifactorial, these cases are presented to encourage further discussion and more rigorous investigation into the validity of a hypothesis that has been derived from this set of cases: that the obesity of a child's caretaker may be an additional risk factor for child maltreatment by starvation.