Thymocyte migration: an affair of multiple cellular interactions?

Savino, Wilson; Martins, Sara; Neves-dos-Santos, S.; Smaniotto, Salete; Ocampo, J.S.P.; Mendes-da-Cruz, Daniella Arêas; Terra-Granado, Eugênia; Kusmenok, O.; Villa‐Verde, Déa Maria Serra

doi:10.1590/s0100-879x2003000800007

Cited by 20 publications

(20 citation statements)

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“…It has been well defined that ligands and receptors of ECM and chemokines as well as adhesion molecules are involved in T-cell migration events [5,16,17,[36][37][38][39]. However, little is known about the influences of hormone in this process.…”

Section: Discussionmentioning

confidence: 99%

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Triiodothyronine Modulates Differential Homing of Recent Thymic Emigrants to Peripheral Lymphoid Organs

et al. 2007

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The functioning of the immune system partially relies on T‐cell exportation from the thymus, the major site of T‐cell differentiation. Although the molecular mechanisms governing this process begin to be elucidated, it is not clear if thyroid hormones can alter the homing of recent thymic emigrants (RTE) to peripheral lymphoid organs. Herein, we investigated whether triiodothyronine (T3) could influence the homing of thymus‐derived T cells. For that we used intrathymic injection of T3 in combination with fluorescein isothiocyanate (FITC) to trace, 16 h later, FITC+ cells, termed RTE, in peripheral lymphoid organs. We observed that T3 stimulated thymocyte export, increasing the frequency of CD4+ RTE and CD8+ RTE in the subcutaneous and mesenteric lymph nodes. By contrast, the relative numbers of CD4+ RTE in the spleen were decreased. T3 also changed the differential distribution pattern of CD4+ RTE, and to a lesser extent CD8+ RTE in the peripheral lymphoid organs. Moreover, the expression of extracellular matrix (ECM) components, such as laminin and fibronectin, which are known to be involved in T‐cell migration, increased in the lymph nodes but not in the spleen following intrathymic T3 treatment. In conclusion, our data correspond to the first demonstration that in vivo treatment with thyroid hormone stimulates thymic T‐cell homing and T‐cell distribution in peripheral lymphoid organs.

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Section: Discussionmentioning

confidence: 99%

“…Several groups have shown that cell-ECM interactions seem to be dependent on integrin surface expression, ECM deposition and degradation [15][16][17]. Furthermore, in vivo stimulation of lymphocyte migration and positioning within tissues seems to occur with chemokines and ECM components acting conjointly [18][19][20][21]41].…”

Section: Introductionmentioning

confidence: 99%

Triiodothyronine Modulates Differential Homing of Recent Thymic Emigrants to Peripheral Lymphoid Organs

et al. 2007

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“…In this vein, it has been shown that TEC are sensitive to fluctuations in laminin: TEC grow faster onto a laminin substrate [55], which also enhances the expression of focal adhesion kinases by these cells [50,51] and augment IL-6 production through a p38 mitogen-activated protein kinase-mediated signaling cascade [56].…”

Section: Ecm Receptors In the Thymus: The Vla Familymentioning

confidence: 99%

“…Last, thymocyte exit to the periphery may also be influenced by VLA-mediated interactions; intrathymic injection of RGDcontaining peptide (recognized by the ␣5␤1/VLA-5 fibronectin receptor) results in a decreased homing of recent thymic emigrants [51]. [55,58,59]), as compared with controls, culture medium alone, or bovine serum albumin (BSA).…”

Section: Ecm Receptors In the Thymus: The Vla Familymentioning

confidence: 99%

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

Savino

Mendes-da-Cruz

Smaniotto

et al. 2004

Journal of Leukocyte Biology

123

122

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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. It is important that although chemokines and ECM proteins can drive thymocyte migration per se, a combined role of these molecules likely concurs for the resulting migration patterns of thymocytes in their various differentiation stages. In this respect, among ECM moieties, there are proteins with opposing functions, such as laminin or fibronectin versus galectin-3, which promote, respectively, adhesion and de-adhesion of thymocytes to the thymic microenvironment. How chemokines and ECM are produced and degraded remains to be more clearly defined. Nevertheless, matrix metalloproteinases (MMPs) likely play a role in the intrathymic ECM breakdown. It is interesting that these molecules also degrade chemokines. Thus, the physiological migration of thymocytes should be conceived as a resulting vector of multiple, simultaneous, or sequential stimuli, involving chemokines, adhesive, and de-adhesive ECM proteins. Moreover, these interactions may be physiologically regulated in situ by matrix MMPs and are influenced by hormones. Accordingly, one can predict that pathological changes in any of these loops may result in abnormal thymocyte migration. This actually occurs in the murine infection by the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. In this model, the abnormal release of immature thymocytes to peripheral lymphoid organs is correlated with the higher migratory response to ECM and chemokines. Lastly, the fine dissection of the mechanisms governing thymocyte migration will provide new clues for designing therapeutic strategies targeting developing T cells. The most important function of the thymus is to generate T lymphocytes, which once leaving the organ, are able to colonize specific regions of peripheral lymphoid organs, the T cell zones, where they can mount and regulate cell-mediated, immune responses. This intrathymic T cell differentiation is a complex sequence of biological events, comprising cell proliferation, differential membrane protein expression, gene rearrangements, massive programmed cell death, and cell migration. In this review, we will focus on the mechanisms involved in controlling the migration of thymocytes, from the entrance of cell precursors into the organ to the exit of mature T cells toward peripheral lymphoid organs. Nevertheless, to better comprehend this issue, it appeared worthwhile to briefly comment on some key aspects of thymocyte differentiation and the tissue context in which it takes place, the thymic microenv...

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“…The thymic microenvironment also influences thymocyte differentiation via cytokines, chemokines, adhesion molecules and extracellular matrix (ECM), most of which modulate not only differentiation but also thymocyte migration patterns [2,3] . The thymic epithelial cell (TEC) network is the major component of the thymic microenvironment, being responsible for positive selection of thymocytes, and for the production of cytokines, chemokines and various ECM components [3] .…”

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confidence: 99%

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

Savino¹

2010

Neuroimmunomodulation

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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.

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Thymocyte migration: an affair of multiple cellular interactions?

Cited by 20 publications

References 37 publications

Triiodothyronine Modulates Differential Homing of Recent Thymic Emigrants to Peripheral Lymphoid Organs

Triiodothyronine Modulates Differential Homing of Recent Thymic Emigrants to Peripheral Lymphoid Organs

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

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

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