RANKL treatment restores thymic function and improves T cell-mediated immune responses in aged mice.

Age-related thymic involution, leading to reduced T cell production, is one of the major causes of immunosenescence. This results in an increased susceptibility to cancers, infections, and autoimmunity and in reduced vaccine efficacy. Here, we identified that the receptor activator of nuclear factor κB (RANK)-RANK ligand (RANKL) axis in the thymus is altered during aging.

Lymphotoxin limits Foxp3 regulatory T cell development from Foxp3 precursors via IL-4 signaling.

Regulatory T cells (T) are critical players of immune tolerance that develop in the thymus via two distinct developmental pathways involving CD25Foxp3 and CD25Foxp3 precursors. However, the mechanisms regulating the recently identified Foxp3 precursor pathway remain unclear. Here, we find that the membrane-bound lymphotoxin αβ (LTαβ) heterocomplex is upregulated during T development upon TCR/CD28 and IL-2 stimulation.

The type 1 diabetes susceptibility locus favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse.

Regulatory T lymphocytes expressing the transcription factor Foxp3 (Tregs) play an important role in the prevention of autoimmune diseases and other immunopathologies. Aberrations in Treg-mediated immunosuppression are therefore thought to be involved in the development of autoimmune pathologies, but few have been documented. Recent reports indicated a central role for Tregs developing during the neonatal period in the prevention of autoimmune pathology.

Toward Grading Subarachnoid Hemorrhage Risk Prediction: A Machine Learning-Based Aneurysm Rupture Score.

Objective: Existing approaches neither provide an accurate prediction of subarachnoid hemorrhage (SAH) nor offer a quantitative comparison among a group of its risk factors. To evaluate the population, hypertension, age, size, earlier subarachnoid hemorrhage, and location (PHASES) and unruptured intracranial aneurysm treatment score (UIATS) scores and develop an Artificial Intelligence-based 5-year and lifetime aneurysmal rupture criticality prediction (ARCP) score for a set of risk factors.

Methods: We design various location-specific and ensemble learning models to develop lifetime rupture risk, employ the longitudinal data to develop a linear regression-based model to predict an aneurysm's growth score, and use the Apriori algorithm to identify risk factors strongly associated with SAH.

IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4Foxp3 regulatory T lymphocytes.

Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell precursors the TCR, co-stimulatory receptors, and cytokine receptors. In absence of IL-2, IL-15 or their receptors, fewer Treg apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had recirculated from the periphery back to the thymus, troubling interpretation of these results.

Recirculating Foxp3 regulatory T cells are restimulated in the thymus under Aire control.

Thymically-derived Foxp3 regulatory T cells (T) critically control immunological tolerance. These cells are generated in the medulla through high affinity interactions with medullary thymic epithelial cells (mTEC) expressing the Autoimmune regulator (Aire). Recent advances have revealed that thymic T contain not only developing but also recirculating cells from the periphery.

Thymocytes trigger self-antigen-controlling pathways in immature medullary thymic epithelial stages.

Interactions of developing T cells with Aire medullary thymic epithelial cells expressing high levels of MHCII molecules (mTEC) are critical for the induction of central tolerance in the thymus. In turn, thymocytes regulate the cellularity of Aire mTEC. However, it remains unknown whether thymocytes control the precursors of Aire mTEC that are contained in mTEC cells or other mTEC subsets that have recently been delineated by single-cell transcriptomic analyses.

The Repertoire of Newly Developing Regulatory T Cells in the Type 1 Diabetes-Prone NOD Mouse Is Very Diverse.

Regulatory T lymphocytes expressing the forkhead/winged helix transcription factor Foxp3 (Treg) play a vital role in the protection of the organism from autoimmune disease and other immunopathologies. The antigen specificity of Treg plays an important role in their in vivo activity. We therefore assessed the diversity of the T-cell receptors (TCRs) for antigen expressed by Treg newly developed in the thymus of autoimmune type 1 diabetes-prone NOD mice and compared it to the control mouse strain C57BL/6.

Regulatory T Cell Heterogeneity in the Thymus: Impact on Their Functional Activities.

Foxp3 regulatory T cells (Treg) maintain the integrity of the organism by preventing excessive immune responses. These cells protect against autoimmune diseases but are also important regulators of other immune responses including inflammation, allergy, infection, and tumors. Furthermore, they exert non-immune functions such as tissue repair and regeneration.

Robust intrathymic development of regulatory T cells in young NOD mice is rapidly restrained by recirculating cells.

Regulatory T lymphocytes (Treg) play a vital role in the protection of the organism against autoimmune pathology. It is therefore paradoxical that comparatively large numbers of Treg were found in the thymus of type I diabetes-prone NOD mice. The Treg population in the thymus is composed of newly developing cells and cells that had recirculated from the periphery back to the thymus.

Antigen-presenting cells and T-lymphocytes homing to the thymus shape T cell development.

Hematopoietic precursors entering the thymus undergo a maturation process leading to the generation of a variety of T cell subsets that migrate to the periphery to perform their effector functions. This maturation process is strictly regulated by multiple interactions of developing T cells with thymic stroma cells. Signals received via the T cell receptor for antigen, co-stimulatory molecules and cytokines will determine, through thymic selection and lineage choice, thymocyte-fate.

Extreme physiological plasticity in a hibernating basoendothermic mammal, .

Physiological plasticity allows organisms to respond to diverse conditions. However, can being too plastic actually be detrimental? Malagasy common tenrecs, , have many plesiomorphic traits and may represent a basal placental mammal. We established a laboratory population of and found extreme plasticity in thermoregulation and metabolism, a novel hibernation form, variable annual timing, and remarkable growth and reproductive biology.