Targeting a disintegrin and metalloprotease (ADAM) 17-CD122 axis enhances CD8 T cell effector differentiation and anti-tumor immunity.

CD8 T cell immune responses are regulated by multi-layer networks, while the post-translational regulation remains largely unknown. Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins. Here, by targeting the sheddase A Disintegrin and Metalloprotease (ADAM)17, we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8 T cells.

The Transcription Factor Zfp335 Promotes Differentiation and Survival of Effector Th1 Cells by Directly Regulating Lmna Expression.

Ag-specific effector CD4+ T cells play a crucial role in defending against exogenous pathogens. However, the mechanisms governing the differentiation and function of IFN-γ-producing effector CD4+ Th1 cells in immune responses remain largely unknown. In this study, we elucidated the pivotal role of zinc finger protein 335 (Zfp335) in regulating effector Th1 cell differentiation and survival during acute bacterial infection.

Effect of Med1 on T cell development and CD4 T cell differentiation in immune response.

Objectives: The differentiation of CD4 T cells is regulated by a complex and fine signaling pathway composed of many molecules during immune response, and the molecular mechanism for regulating T-bet expression is unclear. Mediator complex subunit 1 (Med1) can combine with a variety of co-factors to regulate gene transcription, promote cell proliferation and survival, and affect invariant natural killer T cell (iNKT) development. This study aims to investigate the effect of Med1 on T cell development and CD4 T cell differentiation in immune response.

Single-cell sequencing reveals the evolution of immune molecules across multiple vertebrate species.

Introduction: Both innate and adaptive immune system undergo evolution from low to high vertebrates. Due to the limitation of conventional approaches in identifying broader spectrum of immune cells and molecules from various vertebrates, it remains unclear how immune molecules evolve among vertebrates.

Objectives: Here, we utilized carry out comparative transcriptome analysis in various immune cells across seven vertebrate species.

Med1 Controls Effector CD8 T Cell Differentiation and Survival through C/EBPβ-Mediated Transcriptional Control of T-bet.

Effector CD8 T cells are crucial players in adaptive immunity for effective protection against invading pathogens. The regulatory mechanisms underlying CD8 T cell effector differentiation are incompletely understood. In this study, we defined a critical role of mediator complex subunit 1 (Med1) in controlling effector CD8 T cell differentiation and survival during acute bacterial infection.

The Transcription Factor Zfp335 Promotes Differentiation and Persistence of Memory CD8 T Cells by Regulating TCF-1.

Memory CD8 T cells play an essential role in providing effective and lifelong protection against pathogens. Comprehensive transcriptional and epigenetic networks are involved in modulating memory T cell development, but the molecular regulations of CD8 memory T cell formation and long-term persistence remain largely unknown. In this study, we show that zinc finger protein 335 (Zfp335) is indispensable for CD8 T cell memory establishment and maintenance during acute infections.

Targeting toll-like receptors on T cells as a therapeutic strategy against tumors.

Innate and adaptive immunity synergistically contribute to an effective anti-tumor response. Therapeutics targeting T cells, such as immune checkpoint inhibitors and engineered chimeric antigen receptor (CAR) T cells have shown promising effects in patients with hematologic malignancies. These strategies aim to strengthen T cell activation, proliferation, survival, and/or effector function by altering T cell receptor (TCR) signaling, co-stimulation, and cytokine gene expression.

DExD/H-box helicase 9 intrinsically controls CD8 T cell-mediated antiviral response through noncanonical mechanisms.

Upon virus infection, CD8 T cell accumulation is tightly controlled by simultaneous proliferation and apoptosis. However, it remains unclear how TCR signal coordinates these events to achieve expansion and effector cell differentiation. We found that T cell-specific deletion of nuclear helicase Dhx9 led to impaired CD8 T cell survival, effector differentiation, and viral clearance.

Zinc finger protein Zfp335 controls early T-cell development and survival through β-selection-dependent and -independent mechanisms.

T-cell development in the thymus undergoes the process of differentiation, selective proliferation, and survival from CD4CD8 double negative (DN) stage to CD4CD8 double positive (DP) stage prior to the formation of CD4 helper and CD8 cytolytic T cells ready for circulation. Each developmental stage is tightly regulated by sequentially operating molecular networks, of which only limited numbers of transcription regulators have been deciphered. Here, we identified Zfp335 transcription factor as a new player in the regulatory network controlling thymocyte development in mice.

Arid1a promotes thymocyte development through β-selection-dependent and β-selection-independent mechanisms.

Early T-cell development from CD4  CD8 double-negative (DN) stage to CD4  CD8 double-positive (DP) stage in the thymus is regulated through multiple steps involving a batch of sequentially expressed factors. Our preliminary data and a recent report showed that AT-rich interaction domain 1A (Arid1a) is required for the transition from DN to DP stages, but the mechanism is not fully understood. In this study, we consolidated that conditional deletion of Arid1a in T-cell lineage intrinsically caused developmental blocks from DN3 to DN4 stages, as well as from DN4 to DP stages using both in vivo adoptive T-cell transfer model and in vitro culture system.