Altered galectin-3 distribution and migratory function in the pre-diabetic non-obese diabetic mouse thymus.

Galectin-3 is an endogenous lectin which binds mainly to β-galactosides on the cell surface and extracellular matrix (ECM) glycoproteins. In the thymus, this lectin is constitutively expressed, being involved in thymocyte adhesion, migration, and death. Galectin-3 has been related to type 1 diabetes, an autoimmune disease characterized by pancreatic β-cell destruction mediated by autoreactive T lymphocytes.

Anti-inflammatory role of APRIL by modulating regulatory B cells in antigen-induced arthritis.

APRIL (A Proliferation-Inducing Ligand), a member of the TNF superfamily, was initially described for its ability to promote proliferation of tumor cells in vitro. Moreover, this cytokine has been related to the pathogenesis of different chronic inflammatory diseases, such as rheumatoid arthritis. This study aimed to evaluate the ability of APRIL in regulating B cell-mediated immune response in the antigen-induced arthritis (AIA) model in mice.

Decreased Circulating Levels of APRIL: Questioning Its Role in Diabetes.

Diabetes mellitus is a chronic disease that affects over 382 million people worldwide. Type-1 Diabetes (T1D) is classified as an autoimmune disease that results from pancreatic β-cell destruction and insulin deficiency. Type-2 Diabetes (T2D) is characterized principally by insulin resistance in target tissues followed by decreased insulin production due to β-cell failure.

Lack of galectin-3 speeds Wallerian degeneration by altering TLR and pro-inflammatory cytokine expressions in injured sciatic nerve.

Wallerian degeneration (WD) comprises a series of events that includes activation of non-neuronal cells and recruitment of immune cells, creating an inflammatory milieu that leads to extensive nerve fragmentation and subsequent clearance of the myelin debris, both of which are necessary prerequisites for effective nerve regeneration. Previously, we documented accelerated axon regeneration in animals lacking galectin-3 (Gal-3), a molecule associated with myelin clearance. To clarify the mechanisms underlying this enhanced regeneration, we focus here on the early steps of WD following sciatic nerve crush in Gal-3(-/-) mice.

Caspase-8 and caspase-9 mediate thymocyte apoptosis in Trypanosoma cruzi acutely infected mice.

Trypanosoma cruzi acute infection leads to thymic atrophy, largely as a result of death of immature DP T cells. In a second vein, the glucocorticoid hormone imbalance promotes DP T cell apoptosis in infected mice. Herein, we assessed the involvement of caspase signaling in thymocyte death during T.

Thymus atrophy and double-positive escape are common features in infectious diseases.

The thymus is a primary lymphoid organ in which bone marrow-derived T-cell precursors undergo differentiation, leading to migration of positively selected thymocytes to the T-cell-dependent areas of secondary lymphoid organs. This organ can undergo atrophy, caused by several endogenous and exogenous factors such as ageing, hormone fluctuations, and infectious agents. This paper will focus on emerging data on the thymic atrophy caused by infectious agents.

Thymic microenvironmental alterations in experimentally induced diabetes.

Little is known about the immunologic consequences from endocrine changes observed in diabetes. Since a preserved thymic microenvironment is of critical importance for the T cell development and maturation, we have examined the thymus from alloxan-diabetic mice. An intense thymic atrophy accompanied by changes in histological pattern and in thymocyte subpopulations were observed in diabetic mice.

Differential regional immune response in Chagas disease.

Following infection, lymphocytes expand exponentially and differentiate into effector cells to control infection and coordinate the multiple effector arms of the immune response. Soon after this expansion, the majority of antigen-specific lymphocytes die, thus keeping homeostasis, and a small pool of memory cells develops, providing long-term immunity to subsequent reinfection. The extent of infection and rate of pathogen clearance are thought to determine both the magnitude of cell expansion and the homeostatic contraction to a stable number of memory cells.

Growth hormone modulates migration of developing T cells.

In the context of the cross-talk between the neuroendocrine and immune systems, it is well known that growth hormone (GH) exerts physiological effects in central as well as peripheral compartments of the immune system. GH modulates a variety of thymic functions. For example, GH upregulates proliferation of thymocytes and thymic epithelial cells.

Laminin-211 controls thymocyte--thymic epithelial cell interactions.

Thymocyte differentiation occurs within the thymic microenvironment, consisting of distinct cell types and extracellular matrix (ECM) elements. One of these ECM proteins is laminin. Previous experiments showed that laminin mediates interactions between thymocytes and thymic epithelial cells (TEC) in mice.

Control of human thymocyte migration by Neuropilin-1/Semaphorin-3A-mediated interactions.

It is largely established that molecules first discovered in the nervous system are also found in the immune system. Neuropilin-1 (NP-1) was initially identified to mediate semaphorin-induced chemorepulsion during brain development and is also involved in peripheral T cell/dendritic cell interactions. Herein, we studied NP-1 during T cell development in the human thymus.

Altered expression of galectin-3 induces cortical thymocyte depletion and premature exit of immature thymocytes during Trypanosoma cruzi infection.

During acute infection with Trypanosoma cruzi, the causative agent of Chagas' disease, the thymus undergoes intense atrophy followed by a premature escape of CD4+CD8+ immature cortical thymocytes. Here we report a pivotal role for the endogenous lectin galectin-3 in accelerating death of thymocytes and migration of these cells away from the thymus after T. cruzi infection.

Hypothalamus-pituitary-adrenal axis during Trypanosoma cruzi acute infection in mice.

Functional interactions between neuroendocrine and immune systems are mediated by similar ligands and receptors, which establish a bi-directional communication that is relevant for homeostasis. We investigated herein the hypothalamus-pituitary-adrenal (HPA) axis in mice acutely infected by Trypanosoma cruzi, the causative agent of Chagas' disease. Parasites were seen in the adrenal gland, whereas T.

Growth hormone modulates thymocyte development in vivo through a combined action of laminin and CXC chemokine ligand 12.

Previous evidence indicates that GH modulates thymic cell migration. In this study we approached this issue in vivo, studying thymocyte migration in GH transgenic animals and in normal mice treated intrathymically with GH. Extracellular matrix and chemokines are involved in thymocyte migration.

Phagocytic cells of the thymic reticulum interact with thymocytes via extracellular matrix ligands and receptors.

We previously showed that, in the context of thymic epithelial cells, thymocyte migration is partially controlled by extracellular matrix (ECM)-mediated interactions. Herein we evaluated whether these interactions could be involved in cell migration related events in the context of non-epithelial cells of the thymic microenvironment, the phagocytic cells of the thymic reticulum (PTR). We first showed, by immunocytochemistry, cytofluorometry, and RT-PCR, that PTR produce ECM components, including fibronectin and laminin, and express the corresponding integrin-type receptors, VLA-4, VLA-5, and VLA-6.

Impaired migration of NOD mouse thymocytes: a fibronectin receptor-related defect.

We previously showed intrathymic alterations in non-obese diabetic (NOD) mice, including the appearance of giant perivascular spaces, filled with mature thymocytes, intermingled with an extracellular matrix network. This raised the hypothesis of a defect in thymocyte migration with partial arrest of exiting thymocytes in the perivascular spaces. Herein, we investigated the expression of receptors for fibronectin [very late antigen (VLA)-4 and VLA-5] and laminin (VLA-6), known to play a role in thymocyte migration.

Molecular mechanisms governing thymocyte migration: combined role of chemokines and extracellular matrix.

Cell migration is crucial for thymocyte differentiation, and the cellular interactions involved now begin to be unraveled, with chemokines, extracellular matrix (ECM) proteins, and their corresponding receptors being relevant in such oriented movement of thymocytes. This notion derives from in vitro, ex vivo, and in vivo experimental data, including those obtained in genetically engineered and spontaneous mutant mice. Thymic microenvironmental cells produce both groups of molecules, whereas developing thymocytes express chemokine and ECM receptors.

Trypanosoma cruzi infection modulates intrathymic contents of extracellular matrix ligands and receptors and alters thymocyte migration.

Several T cell abnormalities have been described in the course of acute Trypanosoma cruzi infection in mice, including severe effects on the thymus. In the present study, looking at the expression of extracellular matrix ligands in the thymus, we observed that deposits of fibronectin and laminin increased progressively during the course of infection, reaching a maximum at the peak of parasitemia and thymic atrophy. Concomitantly, membrane expression of fibronectin and laminin receptors (VLA-4, VLA-5 and VLA-6) was also enhanced on thymocyte subsets of infected mice.

Triiodothyronine modulates extracellular matrix-mediated interactions between thymocytes and thymic microenvironmental cells.

Objectives: Thyroid hormones exert immunomodulatory activities and the thymus is one of their target organs. We previously showed that triiodothyronine (T(3)) modulates thymic hormone production and extracellular matrix (ECM) expression by mouse thymic epithelial cells (TEC). This concept is enlarged herein by studying the effects of T(3) in human TEC preparations including primary cultures derived from thymic nurse cell complexes, as well as human and murine TEC lines.

Galectin-3 modulates carbohydrate-dependent thymocyte interactions with the thymic microenvironment.

The process of thymocyte differentiation occurs within the context of the thymic microenvironment, in which T cell precursors interact with thymic microenvironmental cells and extracellular matrix. Here we studied the expression of galectin-3, a beta-galactoside binding lectin, in the thymus of young adult mice. Galectin-3 was found mainly in the medulla and to a lesser extent in the cortex.

Functional insulin-like growth factor-1/insulin-like growth factor-1 receptor-mediated circuit in human and murine thymic epithelial cells.

Interactions between thymocytes and thymic epithelial cell (TEC) can be modulated by growth hormone via insulin-like growth factor-1 (IGF-1). In this study, we showed IGF-1 and IGF-1 receptor mRNA expression by human and murine TEC and thymocytes. Functionally, IGF-1 stimulates extracellular matrix production by human TEC.