Antibody responses in blood and saliva post COVID-19 bivalent booster do not reveal an Omicron BA.4/BA.5- specific response.

Introduction: Current SARS-CoV-2 strains continue to mutate and attempt to evade the antibody response elicited by previous exposures and vaccinations. In September of 2022, the first updated SARS-CoV-2 vaccines, designed to create immune responses specific for the variants circulating in 2022, were approved. These new vaccines, known commonly as the bivalent boost(er), include mRNA that encodes both the original Wuhan-Hu-1 spike protein as well as the spike protein specific to the Omicron BA.

LKB1 isoform expression modulates T cell plasticity downstream of PKCθ and IL-6.

Following activation, CD4 T cells undergo metabolic and transcriptional changes as they respond to external cues and differentiate into T helper (Th) cells. T cells exhibit plasticity between Th phenotypes in highly inflammatory environments, such as colitis, in which high levels of IL-6 promote plasticity between regulatory T (Treg) cells and Th17 cells. Protein Kinase C theta (PKCθ) is a T cell-specific serine/threonine kinase that promotes Th17 differentiation while negatively regulating Treg differentiation.

CD28 Signaling Drives Notch Ligand Expression on CD4 T Cells.

Notch signaling provides an important cue in the mammalian developmental process. It is a key player in T cell development and function. Notch ligands such as Delta-like ligands (DLL) 1, 3, 4, and JAG1, 2 can impact Notch signaling positively or negatively, by -activation or -inhibition.

Notch1 primes CD4 T cells for T helper type I differentiation through its early effects on miR-29.

The transmembrane receptor, Notch1 plays an important role during the differentiation of CD4 T cells into T helper (Th) subsets in the presence of appropriate cytokines, including differentiation into Th1 cells. MicroRNAs have also been shown to be important regulators of immune responses, including negatively regulating cytokine production by Th1 cells. The miR-29 family of microRNAs can act to inhibit tbx21 and ifng transcription, two important pro-inflammatory genes that are abundantly expressed in Th1 cells.

Intracellular Delivery of Anti-pPKCθ (Thr538) via Protein Transduction Domain Mimics for Immunomodulation.

Targeting cellular proteins with antibodies, to better understand cellular signaling pathways in the context of disease modulation, is a fast-growing area of investigation. Humanized antibodies are increasingly gaining attention for their therapeutic potential, but the collection of cellular targets is limited to those secreted from cells or expressed on the cell surface. This approach leaves a wealth of intracellular proteins unexplored as putative targets for antibody binding.

Impact of Notch1 Deletion in Macrophages on Proinflammatory Cytokine Production and the Outcome of Experimental Autoimmune Encephalomyelitis.

Notch signaling is involved in regulating TLR-mediated responses in activated macrophages. In this study, we investigated the impact of Notch signaling in macrophages in an experimental autoimmune encephalomyelitis (EAE) model. To examine the impact of deficiency in Notch signaling in activated macrophages in EAE, an adoptive transfer of activated macrophages derived from Notch1(fl/fl) × Mx1cre(+/-) (Notch1 knockout [N1KO]) or CSL/Rbp-jκ(fl/fl) × Mx1cre(+/-) (CSL/RBP-Jκ KO) mice was performed prior to induction of EAE.

Non-Canonical Notch Signaling Drives Activation and Differentiation of Peripheral CD4(+) T Cells.

Cleavage of the Notch receptor via a γ-secretase, results in the release of the active intra-cellular domain of Notch that migrates to the nucleus and interacts with RBP-Jκ, resulting in the activation of downstream target genes. This canonical Notch signaling pathway has been documented to influence T cell development and function. However, the mechanistic details underlying this process remain obscure.

Notch signaling regulates mouse and human Th17 differentiation.

Th17 cells are known to play a critical role in adaptive immune responses to several important extracellular pathogens. Additionally, Th17 cells are implicated in the pathogenesis of several autoimmune and inflammatory disorders as well as in cancer. Therefore, it is essential to understand the mechanisms that regulate Th17 differentiation.

Potent neutralization of staphylococcal enterotoxin B by synergistic action of chimeric antibodies.

Staphylococcal enterotoxin B (SEB), a shock-inducing exotoxin synthesized by Staphylococcus aureus, is an important cause of food poisoning and is a class B bioterrorism agent. SEB mediates antigen-independent activation of a major subset of the T-cell population by cross-linking T-cell receptors (TCRs) with class II major histocompatibility complex (MHC-II) molecules of antigen-presenting cells, resulting in the induction of antigen independent proliferation and cytokine secretion by a significant fraction of the T-cell population. Neutralizing antibodies inhibit SEB-mediated T-cell activation by blocking the toxin's interaction with the TCR or MHC-II and provide protection against the debilitating effects of this superantigen.

Pathways contributing to development of spontaneous mammary tumors in BALB/c-Trp53+/- mice.

Mutation and loss of function in p53 are common features among human breast cancers. Here we use BALB/c-Trp53+/- mice as a model to examine the sequence of events leading to mammary tumors. Mammary gland proliferation rates were similar in both BALB/c-Trp53+/- mice and wild-type controls.

Inhibitors of gamma-secretase block in vivo and in vitro T helper type 1 polarization by preventing Notch upregulation of Tbx21.

Notch receptors are processed by gamma-secretase acting in synergy with T cell receptor signaling to sustain peripheral T cell activation. Activated CD4+ T cells differentiate into T helper type 1 (TH1) or TH2 subsets. Molecular cues directing TH1 differentiation include expression of the TH1-specific transcription factor T-bet, encoded by Tbx21.