Intrathymic T Cell Migration Is a Multivectorial Process under a Complex Neuroendocrine Control

Abstract

The thymus is responsible for normal T cell development, a process that includes cell proliferation, death, migration, and T cell receptor gene rearrangements. Moreover, it depends on interactions between developing thymocytes and thymic microenvironmental cells. Along with differentiation, thymocytes migrate and such oriented movement is regulated by several molecular interactions, comprising extracellular matrix (ECM) elements and chemokines. We postulated that intrathymic T cell migration is a multivectorial process; each individual vector being represented by a given molecular interaction. In vivo and in vitro experiments revealed that migration of developing thymocytes, including the export of mature T cells, is upregulated by hormones, such as growth hormone and triiodothyronine, through the modulation of ECM-mediated interactions, associated or not with the chemokine CXCL12. Recent data revealed that molecular interactions typically found in the nervous system also affect intrathymic T cell migration. Semaphorin-3A, a soluble member of the semaphorin family, is involved in the control of human thymocyte migration, bearing a chemorepulsive role. Such an effect is partially due to its downregulatory effect upon the interactions mediated by fibronectin and laminin, as well as CXCL12. These data unravel a complex neuroendocrine control intrathymic T cell migration, involving both endocrine and paracrine molecular interactions.

MicroRNAs: Biological Regulators in Pathogen–Host Interactions

“…The infection of B6 mice by T. cruzi leads to increased levels of miR-10a in thymic epithelial cells (TEC) involved in intrathymic T cell differentiation, which can be caused by TGF-β signaling and impact thymus atrophy during infection [124,125].…”

Hormonal control of T-cell development in health and disease

“…Importantly, hormones can control thymus physiology, including T-cell development, and the thymus itself can also affect endocrine axes. 1 Investigations in the 1970s and 1980s showed that neonatal thymectomy generated abnormal development of secondary sexual organs, 2 and that a given cell-mediated antigen stimulation triggered a feedback response involving the production of glucocorticoids and IL-1. 3 During the 1980s, the existence of a common syntax in neuroendocrine and lymphoid tissues was also proposed.…”

Tumor-induced thymic atrophy: Alteration in interferons and Jak/Stats signaling pathways

“…The thymus is the primary lymphoid organ where bone marrow-derived T cells precursors differentiate and proliferate, ultimately leading to migration of positively selected thymocytes to the peripheral organs where they respond to antigen stimulation and undergo effector differentiation (1,2). It has been well defined that the thymus provides an optimal and essential microenvironment for T cell development and maturation (3).…”