The highway code of T cell trafficking

Marelli‐Berg, Federica M.; Cannella, Laura; Dazzi, Francesco; Mirenda, Vincenzo

doi:10.1002/path.2269

Cited by 87 publications

(84 citation statements)

References 125 publications

(152 reference statements)

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“…11 In this study, we show that IL-7 selectively induces expression and functional activation of integrin ␣4␤7, the main intestinal lymphocyte homing receptor, [11][12][13][14] both in vitro and in vivo. This effect occurs predominantly in naive T cells, which indeed showed a marked and selective in vivo homing to the intestinal compartment of humanized mice after treatment with IL-7.…”

Section: Introductionmentioning

confidence: 66%

IL-7 induces expression and activation of integrin α4β7 promoting naive T-cell homing to the intestinal mucosa

Cimbro

Vassena

Arthos

et al. 2012

Blood

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Interleukin-7 (IL-7 IntroductionInterleukin-7 (IL-7) is a nonredundant cytokine that plays an essential role in lymphopoiesis and in the homeostasis of the T-lymphoid compartment in adults. 1,2 IL-7 is produced at constitutive levels by stromal cells resident in various organs, as well as by thymic and intestinal epithelial cells. 3 Under physiologic conditions, IL-7 supports long-term survival of naive and memory T cells without inducing proliferation, thereby maintaining the regular size of the T-cell pool. 2 Under conditions of lymphopenia, the concentration of IL-7 rises to suprahomeostatic levels (as reflected by plasma concentrations greater than 10 pg/mL) that induce proliferation of both naive and memory T cells with the aim of reconstituting the physiologic T-cell pool, a process commonly referred to as lymphopenia-induced proliferation. 2 Because of these unique biologic properties and lack of side effects typically associated with other cytokines such as IL-2, IL-7 is currently under clinical evaluation as an immune-reconstitution agent in various forms of immunodeficiencies, including those associated with AIDS and cancer. 4 Short-term courses of IL-7 administration in humans and macaques were shown to result in proliferation of both CD4 ϩ and CD8 ϩ T cells, with preferential expansion of naive T cells associated with increased diversification of the T-cell receptor (TCR) repertoire. [5][6][7][8][9] Remarkably, injection of IL-7 induces a rapid, albeit transient, reduction in circulating lymphocyte counts compatible with redistribution of these cells to peripheral tissues. 6,7 This phenomenon may reflect events that occur naturally when endogenous IL-7 increases to suprahomeostatic levels in response to lymphopenia. Although data obtained in macaques have suggested that lymph nodes, parts of the intestine, and the skin may be homing sites for T cells after IL-7 injection, 10 the anatomical sites where homeostatic processes take place and the molecular mechanisms underlying the IL-7-driven homing and proliferation of T cells in peripheral tissues remain largely undefined.The circulation of T cells from blood to secondary lymphoid organs and other tissues is governed by a complex network of tissue-homing mechanisms, which mainly relies on integrins, chemokine receptors, and their specific ligands. 11 In this study, we show that IL-7 selectively induces expression and functional activation of integrin ␣4␤7, the main intestinal lymphocyte homing receptor, [11][12][13][14] both in vitro and in vivo. This effect occurs predominantly in naive T cells, which indeed showed a marked and selective in vivo homing to the intestinal compartment of humanized mice after treatment with IL-7. The evidence presented in this study provides a mechanism for the rapid reduction of circulating T cells after in vivo IL-7 administration and suggests that ␣4␤7-mediated gut homing of naive T cells may be a fundamental step in the IL-7-driven T-cell reconstitution of lymphopenic hosts. Methods Cells and culture conditionsPeriphe...

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Section: Introductionmentioning

confidence: 66%

IL-7 induces expression and activation of integrin α4β7 promoting naive T-cell homing to the intestinal mucosa

Cimbro

Vassena

Arthos

et al. 2012

Blood

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“…Upon antigenic stimulation, T-cells are reprogrammed into memory T-cells to respond to inflammation-induced chemokines such as CXCL10, which allow them to gain access to non-lymphoid tissue, where they perform their effector function, which can lead to nonspecific tissue damage if it is not controlled (Marelli-Berg et al, 2008). The proliferative potential of memory T-cells is considerably reduced compared with that of naïve T-cells and is therefore unlikely to require stringent regulation by CD31.…”

Section: Molecular Mechanisms Of Differential Cd31 Activity In Naïve mentioning

confidence: 99%

An immunologist's guide to CD31 function in T-cells

Marelli‐Berg

Clément

Mauro

et al. 2013

Journal of Cell Science

118

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SummaryAlthough it is expressed by all leukocytes, including T-, B-lymphocytes and dendritic cells, the immunoglobulin-like receptor CD31 is generally regarded by immunologists as a marker of endothelial cell lineage that lacks an established functional role in adaptive immunity. This perception has recently been challenged by studies that reveal a key role for this molecule in the regulation of T-cell homeostasis, effector function and trafficking. The complexity of the biological functions of CD31 results from the integration of its adhesive and signaling functions in both the immune and vascular systems. Signaling by means of CD31 is induced by homophilic engagement during the interactions of immune cells and is mediated by phosphatase recruitment or activation through immunoreceptor tyrosine inhibitory motifs (ITIMs) that are located in its cytoplasmic tail. Loss of CD31 function is associated with excessive immunoreactivity and susceptibility to cytotoxic killing. Here, we discuss recent findings that have brought to light a non-redundant, complex role for this molecule in the regulation of T-cell-mediated immune responses, with large impact on our understanding of immunity in health and disease.

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“…Productive interaction of effector T cells with MHC:peptide complexes on APCs is required for their reactivation in the course of an immune response (24,25). This feature was investigated using Ag-loaded thymocytes, because the latter are traditionally used as APCs when restimulating gpMBP-specific rat effector T cells in culture (17,18).…”

Section: Diminished Interaction Of Effector T Cells With Apcs After Gmentioning

confidence: 99%

Glucocorticoids Induce Effector T Cell Depolarization via ERM Proteins, Thereby Impeding Migration and APC Conjugation

Müller

Fischer

Tischner

et al. 2013

The Journal of Immunology

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Glucocorticoids (GCs) repress lymphocyte function by controlling gene expression. In this study, we investigated Ag-specific effector T cells and provide evidence that GCs also modulate these cells’ cytoskeletal architecture by nongenomic mechanisms. Following GC treatment, effector T cells rapidly lose their polarized morphology, which impedes both their migratory capacity and their interaction with APCs. The cytoskeleton rearrangements are preceded by an activation of ezrin–radixin–moesin proteins, which transiently increases the cellular rigidity but seems to occur independently of altered tyrosine phosphorylation. Phospholipase C activity is critically involved in mediating these nongenomic effects, because its inhibition prevents both T cell depolarization and ezrin–radixin–moesin phosphorylation after GC exposure. GC administration in vivo induced similar morphological changes in effector T cells as observed in vitro, suggesting that the above process plays a role in modulating inflammatory diseases. Taken together, our findings identify a novel mechanism through which GCs rapidly repress T cell function independently of gene transcription.

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The highway code of T cell trafficking

Cited by 87 publications

References 125 publications

IL-7 induces expression and activation of integrin α4β7 promoting naive T-cell homing to the intestinal mucosa

IL-7 induces expression and activation of integrin α4β7 promoting naive T-cell homing to the intestinal mucosa

An immunologist's guide to CD31 function in T-cells

Glucocorticoids Induce Effector T Cell Depolarization via ERM Proteins, Thereby Impeding Migration and APC Conjugation

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