“Galectin‐1 Induces Central and Peripheral Cell Death:Implications in T‐Cell Physiopathology”

Abstract

The immune system has a remarkable capacity to maintain a state of equilibrium even as it responds to a diverse array of foreign proteins and despite its contact exposure to self-antigens. Apoptosis is one of the mechanisms aimed at preserving the homeostasis after the completion of an immune response, thus returning the immune system to a basal state and warranting the elimination of autoagressive cells in both central and peripheral lymphoid organs. Targeted deletions in critical genes involved in the apoptotic death machinery together with natural spontaneous mutations have clearly shown the importance of apoptosis in the regulation of the immune response. This complex scenario of stimulatory and inhibitory genes has been enriched with the finding that galectin-1, a 14.5 kDa [3-galactoside-binding protein, is able to induce apoptosis of immature cortical thymocytes and mature T cells by cross-linking cell surface glycoconjugates. Galectin-1 is present not only in central and peripheral lymphoid organs, but also at sites of immune privilege. In the present article we will discuss the implications of galectin-1-induced apoptosis in T-cell physiopathology in an attempt to validate its therapeutic potential in autoimmune and inflammatory diseases.Keywords: galectin-1, apoptosis, immunomodulation, macrophages, autoimmunity INTRODUCTION Death, along with growth and differentiation, is a critical part of the life cycle of the cell. Homeostasis control of cell number is thought to be the result of the dynamic balance between cell proliferation and cell death. It is only in the past ten years, that the attention has been focused on the physiological occurrence of cell death and its role in the homeostasis.Apoptosis or programmed cell death, is a phenomenon that plays a crucial role in a myriad of physiological and pathological processes. This review will briefly cover some relevant aspects of programmed cell death in the immune system in an attempt to provide valuable information about new molecules responsible for triggering death signals, such as galectin-1. The implications of this protein will be discussed in the context of T cell physiology and the regulation of central and peripheral tolerance. Finally, novel and intriguing findings will also be discussed implicating the use of this carbohydrate-binding protein in the treatment of autoimmune and inflammatory diseases.

Galectin-1 Mediates Radiation-Related Lymphopenia and Attenuates NSCLC Radiation Response

“…Gal-1 is also produced by tumor-associated endothelial cells (19), however, our tumor model, which controls for host Gal-1 with Gal1 −/− mice, suggests that tumor Gal-1 alone is responsible for the drop in circulating T cells following RT. Gal-1-mediated T cell suppression at the periphery has been shown in other contexts, including the maintenance of central T cell tolerance (22). Here, we found that tumor secreted Gal-1 also drives the depletion of peripheral T cells after RT.…”

The investigation of galectin-3 in diseases of the thyroid gland

“…It seems to play an important role in a number of biological and pathological processes. It is a regulating component of the cell cycle (an apoptosis inhibitor, it stimulates cell proliferation in which process gal3 shows an increased expression and nuclear localization) (1 -5), it regulates cell -cell and cellmatrix interaction, adhesion (major non-integrin laminin binding protein) (2, 5 -7) and migration, it has a role in inflammation (8), neoplastic transformation (9), metastatization and in reparation of the damaged cell. Gal3 is expressed in various tissues and cell types (e.g.…”

Molecular pathogenesis of craniopharyngioma: switching from a surgical approach to a biological one

“…Indeed, mammalian galectins, which are betagalactoside-binding proteins, can also exert a notable influence on growth regulation through proapoptotic (for example, galectin-1) or antiapoptotic (for example, galectin-3) mechanisms. 9,22,42 Analogous to MIF, galectin-3 levels of expression were significantly lower in rapidly recurrent craniopharyngiomas. 23 In view of the antiapoptotic role of galectin-3, its low level of expression in recurring craniopharyngiomas seems to be related more to its role in phagocytosis.…”