Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self

Sakaguchi, Shimon

doi:10.1038/ni1178

Cited by 2,411 publications

(1,994 citation statements)

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“…They are therefore crucial for the maintenance of immune self‐tolerance and homeostasis (for review, see Sakaguchi et al ., 2008). The most studied Treg cells are the CD4 + CD25 hi FoxP3 + that are required for self‐tolerance and a proper immune response to pathogens (Sakaguchi, 2005). Recently, Ye et al .…”

Section: Cellular Senescence and Immunity In Tissue Homeostasismentioning

confidence: 99%

Cellular senescence impact on immune cell fate and function

et al. 2016

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SummaryCellular senescence occurs not only in cultured fibroblasts, but also in undifferentiated and specialized cells from various tissues of all ages, in vitro and in vivo. Here, we review recent findings on the role of cellular senescence in immune cell fate decisions in macrophage polarization, natural killer cell phenotype, and following T‐lymphocyte activation. We also introduce the involvement of the onset of cellular senescence in some immune responses including T‐helper lymphocyte‐dependent tissue homeostatic functions and T‐regulatory cell‐dependent suppressive mechanisms. Altogether, these data propose that cellular senescence plays a wide‐reaching role as a homeostatic orchestrator.

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Section: Cellular Senescence and Immunity In Tissue Homeostasismentioning

confidence: 99%

Cellular senescence impact on immune cell fate and function

et al. 2016

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“…CD25 + CD4 + Treg play a central role in the maintenance of immunological homeostasis and self tolerance [1]. They were initially identified in lymphoid tissues including thymus, spleen and LN as well as in peripheral blood.…”

Section: Introductionmentioning

confidence: 99%

Distinctive role of CCR7 in migration and functional activity of naive‐ and effector/memory‐like Treg subsets

et al. 2007

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Foxp3 + CD25 + CD4 + Treg play a fundamental role in the maintenance of self tolerance and the control of inflammatory reactions. Previous data demonstrated a division of labor between naive-and effector/memory-like Treg subsets, which is largely based on their lymph node-recirculating and inflammation-seeking migration behavior, respectively. The chemokine receptor CCR7 is expressed on both types of Treg subsets, albeit at different levels. Whether it fulfills similar or distinct roles in these subsets has not been studied so far. We here show that the recirculation of naive-like Treg through LN and, to some extent, the gut is dependent on CCR7. Lack of CCR7 not only prevents recirculation, but also almost completely abolishes the ability of naive-like Treg to control the priming phase of an immune response. In contrast, CCR7 deficiency in effector/memory-like Treg promotes their accumulation in inflamed sites, compatible with a role of CCR7 for exit from the tissue. Local Treg accumulation was accompanied by an enhanced suppression of inflammation. Together, our findings provide conclusive evidence that CCR7 expression on Treg differentially controls in vivo function of the naive-and effector/memory-like subsets.

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“…CD25 + CD4 + Treg play a central role in the maintenance of immunological homeostasis and self-tolerance [29]. Treg are by no means homogeneous, but rather can be subdivided into naïve-like subsets, which preferentially recirculate through lymphoid tissues, and effector/memory subsets, which efficiently migrate into peripheral sites and sites of ongoing immune responses [30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

“…However, the factors, which are involved in the generation of skin-specific T cell homing in vivo, are largely unknown, although important roles for cytokines including IL-12 and TGF-b have been suggested from in vitro studies [26][27][28]. CD25 + CD4 + Treg play a central role in the maintenance of immunological homeostasis and self-tolerance [29]. Treg are by no means homogeneous, but rather can be subdivided into naïve-like subsets, which preferentially recirculate through lymphoid tissues, and effector/memory subsets, which efficiently migrate into peripheral sites and sites of ongoing immune responses [30][31][32][33].…”

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confidence: 99%

Induction of organ‐selective CD4⁺ regulatory T cell homing

et al. 2007

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Compelling evidence suggests that Foxp3 + CD25 + CD4 + Treg play a fundamental role in immunoregulation. We have previously demonstrated that Treg have to enter peripheral tissues to suppress ongoing inflammation. However, relatively little is known about how Treg acquire the expression of homing receptors required for tissue-or inflammationspecific migration. Migratory properties of conventional naïve T cells are shaped by the tissue microenvironment and organ-specific dendritic cells during priming. Here, we show that this basic concept also holds true for CD25 + CD4 + Treg: Priming of Treg within peripheral LN led to the expression of selectin ligands, which facilitate migration into inflamed skin, whereas activation within mesenteric LN led to induction of the integrin a 4 b 7 , which is required for migration into mucosal tissues. Furthermore, we could establish in vitro culture systems containing either dendritic cells from mesenteric and peripheral LN, or retinoic acid and IL-12 as polarizing compounds to induce mucosa-and skin-seeking Treg, respectively. Together, our results demonstrate that Treg, similarly to conventional T cells, can be configured with organ-selective homing properties allowing efficient targeting into distinct tissues. IntroductionMigration of T cell subsets to different tissues is determined by the combined expression of adhesion molecules and chemokine receptors (CCR) on the cell surfaces [1][2][3][4]. Among these homing receptors (HR), the integrin a 4 b 7 [5,6] and the chemokine receptor CCR9 [7][8][9] mediate the homing of T cell subsets to GALT such as mesenteric LN (mLN) and Peyer's patches (PP) and to the small intestinal lamina propria and the mucosal epithelium. In contrast, T cell trafficking to the skin is mediated by P-(P-lig) and E-(E-lig) selectin ligands [10,11] as well as .Recently, a number of studies have described that antigen-dependent differentiation of naïve T cells in lymphoid organs leads to the generation of effector T cells exhibiting a capacity to enter peripheral extralymphoid tissues [2]. Effector T cells generated in different lymphoid organs display distinct tissue tropism, which is regulated by an organ-specific induction of adhesion molecules and chemokine receptors during T cell priming [4,[15][16][17][18][19][20][21]. For example, T cells activated in mLN and PP draining the gut acquire high levels of the integrin a 4 b 7 , whereas activation in skin-draining peripheral LN (pLN) results in the upregulation of selectin ligands such as P-lig. Tissuespecific DC have been shown in a number of in vitro and in vivo studies to be involved in the instruction of naïve T cells [4,[17][18][19][20][22][23][24] reported that GALT DC were capable of converting metabolites of dietary vitamin A into retinoic acid (RA), which in turn induced T cell expression of a 4 b 7 and CCR9, leading to the generation of gut-tropic T cells. However, the factors, which are involved in the generation of skin-specific T cell homing in vivo, are largely unknown, although important ...

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Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self

Cited by 2,411 publications

References 104 publications

Cellular senescence impact on immune cell fate and function

Cellular senescence impact on immune cell fate and function

Distinctive role of CCR7 in migration and functional activity of naive‐ and effector/memory‐like Treg subsets

Induction of organ‐selective CD4⁺ regulatory T cell homing

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Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self

Cited by 2,411 publications

References 104 publications

Cellular senescence impact on immune cell fate and function

Cellular senescence impact on immune cell fate and function

Distinctive role of CCR7 in migration and functional activity of naive‐ and effector/memory‐like Treg subsets

Induction of organ‐selective CD4+ regulatory T cell homing

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Induction of organ‐selective CD4⁺ regulatory T cell homing