IL-2-induced Stat3 Signaling is Critical for Effector Treg Cell Programming.

Maintenance of immune homeostasis to the intestinal mictrobiota is dependent on a population of effector regulatory T (eTreg) cells that develop from microbiota-reactive induced (i)Treg cells. A cardinal feature of eTreg cells is their production of IL-10, which plays a non-redundant role in immune tolerance of commensal microbes. Here, we identify an unexpected role for IL-2-induced Stat3 signaling to program iTreg cells for eTreg cell differentiation and transcriptional competency.

Outlier Expression of Isoforms by Targeted or Total RNA Sequencing Identifies Clinically Significant Genomic Variants in Hematolymphoid Tumors.

Recognition of aberrant gene isoforms due to DNA events can impact risk stratification and molecular classification of hematolymphoid tumors. In myelodysplastic syndromes, KMT2A partial tandem duplication (PTD) was one of the top adverse predictors in the International Prognostic Scoring System-Molecular study. In B-cell acute lymphoblastic leukemia (B-ALL), ERG isoforms have been proposed as markers of favorable-risk DUX4 rearrangements, whereas deletion-mediated IKZF1 isoforms are associated with adverse prognosis and have been extended to the high-risk IKZF1 signature defined by codeletions, including PAX5.

T-B Collaboration in Autoimmunity, Infection, and Transplantation.

We have attempted here to provide an up-to-date review of the collaboration between helper T cells and B cells in response to protein and glycoprotein antigens. This collaboration is essential as it not only protects from many pathogens but also contributes to a litany of autoimmune and immune-mediated diseases.

Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy.

Kidney transplant recipients are at particular risk for developing tumors, many of which are now routinely treated with immune checkpoint inhibitors (ICIs); however, ICI therapy can precipitate transplant rejection. Here, we use TCR sequencing to identify and track alloreactive T cells in a patient with melanoma who experienced kidney transplant rejection following PD-1 inhibition. The treatment was associated with a sharp increase in circulating alloreactive CD8 T cell clones, which display a unique transcriptomic signature and were also detected in the rejected kidney but not at tumor sites.

Surgical Management in Herpes Simplex Encephalitis: Illustrative Case Report and Systematic Review of the Literature.

Background: Herpes simplex virus (HSV) is a common cause of viral encephalitis and can result in refractory seizures. Although HSV encephalitis (HSVE) is treated primarily with acyclovir, surgery can play a role in medically intractable cases.

Objective: To systematically review cases describing surgery for the treatment of severe HSVE.

"ILC2 it, but I can't promise anything".

A conditional knockout system permitting deletion of ILC2 cells reveals non-redundant roles in eosinophil recruitment and helminth clearance.

Hemolysis Index and Potassium Reporting.

Objectives: In vitro hemolysis generates a spurious increase in potassium. Roche Diagnostics recently revised its recommended guidelines for potassium reporting on cobas analyzers. By dramatically reducing the allowable degree of hemolysis, these guidelines would increase specimen rejection rates.

Emerging Complexity in CD4T Lineage Programming and Its Implications in Colorectal Cancer.

The intestinal immune system has the difficult task of protecting a large environmentally exposed single layer of epithelium from pathogens without allowing inappropriate inflammatory responses. Unmitigated inflammation drives multiple pathologies, including the development of colorectal cancer. CD4T cells mediate both the suppression and promotion of intestinal inflammation.

Ruptured Suprasellar Dermoid Cyst Treated With Lumbar Drain to Prevent Postoperative Hydrocephalus: Case Report and Focused Review of Literature.

Ruptured intracranial dermoid cysts are extremely rare. Standard treatment consists of endonasal decompression or craniotomy with evacuation and copious irrigation of subarachnoid spaces to remove any disseminated cystic contents. Disseminated fat particles in the subarachnoid space may be the cause of further sequalae, including the subsequent development of chemical meningitis and hydrocephalus.

Radiation-induced intracranial osteosarcoma of the anterior skull base after treatment of esthesioneuroblastoma.

Esthesioneuroblastoma (ENB) is an uncommon sinonasal cancer of the olfactory neuroepithelium that is typically treated with surgical resection followed by radiation therapy. Radiation-induced intracranial osteosarcoma of the skull base is a rare but devastating long-term complication of radiation therapy in this region. Here, we present a case of an 82-year-old patient who developed radiation-induced osteosarcoma of the anterior skull base and paranasal sinuses 10 years after radiation therapy following resection of an ENB.

T17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity.

Acting in concert with TGF-β, interleukin-6 (IL-6) signaling induces T helper 17 (T17) cell development by programming T17-related genes via signal transducers and activators of transcription 3 (STAT3). A role for IL-6 signaling beyond the inductive phase of T17 cell development has not been defined because IL-23 signaling downstream of T17 cell induction also activates STAT3 and is thought responsible for T17 cell maintenance. Here, we find that IL-6 signaling is required for both induction and maintenance of mouse T17 cells; IL-6Rα-deficient T17 cells rapidly lost their T17 phenotype and did not cause disease in two models of colitis.

Insulin-Like Growth Factors Are Key Regulators of T Helper 17 Regulatory T Cell Balance in Autoimmunity.

Appropriate balance of T helper 17 (Th17) and regulatory T (Treg) cells maintains immune tolerance and host defense. Disruption of Th17-Treg cell balance is implicated in a number of immune-mediated diseases, many of which display dysregulation of the insulin-like growth factor (IGF) system. Here, we show that, among effector T cell subsets, Th17 and Treg cells selectively expressed multiple components of the IGF system.

A novel in situ multiplex immunofluorescence panel for the assessment of tumor immunopathology and response to virotherapy in pediatric glioblastoma reveals a role for checkpoint protein inhibition.

Immunotherapy with oncolytic herpes simplex virus-1 therapy offers an innovative, targeted, less-toxic approach for treating brain tumors. However, a major obstacle in maximizing oncolytic virotherapy is a lack of comprehensive understanding of the underlying mechanisms that unfold in CNS tumors/associated microenvironments after infusion of virus. We demonstrate that our multiplex biomarker screening platform comprehensively informs changes in both topographical location and functional states of resident/infiltrating immune cells that play a role in neuropathology after treatment with HSV G207 in a pediatric Phase 1 patient.

Preventing dysbiosis of the neonatal mouse intestinal microbiome protects against late-onset sepsis.

Late-onset sepsis (LOS) is thought to result from systemic spread of commensal microbes from the intestines of premature infants. Clinical use of probiotics for LOS prophylaxis has varied owing to limited efficacy, reflecting an incomplete understanding of relationships between development of the intestinal microbiome, neonatal dysbiosis and LOS. Using a model of LOS, we found that components of the developing microbiome were both necessary and sufficient to prevent LOS.

Differential IL-2 expression defines developmental fates of follicular versus nonfollicular helper T cells.

In response to infection, naïve CD4 T cells differentiate into two subpopulations: T follicular helper (T) cells, which support B cell antibody production, and non-T cells, which enhance innate immune cell functions. Interleukin-2 (IL-2), the major cytokine produced by naïve T cells, plays an important role in the developmental divergence of these populations. However, the relationship between IL-2 production and fate determination remains unclear.

IL-21 and IL-6 are critical for different aspects of B cell immunity and redundantly induce optimal follicular helper CD4 T cell (Tfh) differentiation.

Cytokines are important modulators of lymphocytes, and both interleukin-21 (IL-21) and IL-6 have proposed roles in T follicular helper (Tfh) differentiation, and directly act on B cells. Here we investigated the absence of IL-6 alone, IL-21 alone, or the combined lack of IL-6 and IL-21 on Tfh differentiation and the development of B cell immunity in vivo. C57BL/6 or IL-21(-/-) mice were treated with a neutralizing monoclonal antibody against IL-6 throughout the course of an acute viral infection (lymphocytic choriomeningitis virus, LCMV).

Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150).

CD4 T cell help is critical for the generation and maintenance of germinal centers (GCs), and T follicular helper (T(FH)) cells are the CD4 T cell subset required for this process. Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP [SH2D1A]) expression in CD4 T cells is essential for GC development. However, SAP-deficient mice have only a moderate defect in T(FH) differentiation, as defined by common T(FH) surface markers.

Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation.

Effective B cell-mediated immunity and antibody responses often require help from CD4+ T cells. It is thought that a distinct CD4+ effector T cell subset, called T follicular helper cells (T(FH)), provides this help; however, the molecular requirements for T(FH) differentiation are unknown. We found that expression of the transcription factor Bcl6 in CD4+ T cells is both necessary and sufficient for in vivo T(FH) differentiation and T cell help to B cells in mice.