Differences in Expression Level of Helios and Neuropilin-1 Do Not Distinguish Thymus-Derived from Extrathymically-Induced CD4+Foxp3+ Regulatory T Cells

Szurek, Edyta; Cebula, Anna; Wojciech, Łukasz; Pietrzak, Maciej; Rempała, Grzegorz A.; Kisielow, Paweł; Ignatowicz, Leszek

doi:10.1371/journal.pone.0141161

Cited by 132 publications

(125 citation statements)

References 69 publications

(92 reference statements)

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“…In addition, many subphenotypes of T regs have been identified in human and rodent models based on the expression of different markers, identifying profiles associated with a major specific suppressive function, migration pattern and/or activation, suggestive of their heterogeneous nature. Although other markers, such as Helios (a transcription factor of the Ikaros family) and Neuropilin-1 (Nrp1, a surface molecule), have been introduced, their use is still controversial [4,5]. Fortunately, tT regs could be distinguished from pT regs through the identification of a non-coding sequence within the FOXP3 locus named TSDR (T reg -specific demethylated region) that is completely demethylated on tT regs , contrary to pT regs or T cons in which TSDR is methylated.…”

Section: Regulatory Cd4mentioning

confidence: 99%

Phenotypical characterization of regulatory T cells in humans and rodents

Rodríguez‐Perea

Arcia

Rueda

et al. 2016

Clinical and Experimental Immunology

139

122

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SummaryRegulatory T cells (T regs ) constitute a fascinating subpopulation of CD4 1 T cells due to their ability to limit the immune response against self and non-self antigens. Murine models and antibodies directed against surface and intracellular molecules have allowed elucidation of the mechanisms that govern their development and function. However, these markers used to their classification lack of specificity, as they can be expressed by activated T cells. Similarly, there are slight differences between animal models, in steady state and pathological conditions, anatomical localization and strategy of analysis by flow cytometry. Here, we revised the most common markers utilized for T reg typification by flow cytometry such as CD25, forkhead box protein 3 (FoxP3) and CD127, along with our data obtained in different body compartments of humans, mice and rats. Furthermore, we revised and determined the expression of other molecules important for the phenotypical characterization of T reg cells. We draw attention to the drawbacks of those markers used in chronic states of inflammation. However, until a specific marker for the identification of T regs is discovered, the best combination of markers will depend upon the tissue or the degree of inflammation from which T regs derive.

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Section: Regulatory Cd4mentioning

confidence: 99%

Phenotypical characterization of regulatory T cells in humans and rodents

Rodríguez‐Perea

Arcia

Rueda

et al. 2016

Clinical and Experimental Immunology

139

122

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“…This is in large part due to a lack of specific markers that would allow the identification and distinction of pTreg and tTreg. Neuropilin-1 (Nrp-1), a semaphorin receptor, was reported to be exclusively expressed by tTreg and not by pTreg [13] , but its usefulness to distinguish between these two populations is still controversial [14] . In fact, Nrp-1 expression is also acquired by pTreg upon strong activation and inflammatory conditions [13] .…”

Section: Functions Of Ttreg and Ptregmentioning

confidence: 99%

“…It appears therefore that the peripheral differentiation of pTreg drops with age because of a combination of reduced thymic output and potentially thymocyte-intrinsic factors. Unfortunately, in vivo longitudinal studies of the generation and function of pTreg are limited because of the lack of a reliable marker that identifies this population [14] .…”

Section: Aging and Treg Productionmentioning

confidence: 99%

Age-Dependent Changes in Regulatory T Lymphocyte Development and Function: A Mini-Review

Darrigues¹,

Meerwijk²,

Romagnoli³

2017

Gerontology

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The generation and function of immuno-suppressive regulatory T lymphocytes (Treg), which can differentiate in the thymus (tTreg) or in the periphery (pTreg), are regulated in an age-dependent manner. tTreg are produced at high levels in the first weeks of age, when they expand and colonize secondary lymphoid organs and peripheral tissues to protect the organism from autoimmune diseases and to promote tissue repair. Once this population of Treg is operational in the periphery, at puberty, thymic output of Treg declines, but self-reactive tTreg generated early on in life are maintained over time and play a major role in preserving homeostasis of the immune system. Extra-thymic pTreg differentiation declines later on in life. pTreg generated throughout life mainly protect the organism from chronic inflammation and the semi-allogeneic fetus from rejection. In this review, age-dependent modulation of the production and function of these two populations of Treg is described.

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“…[33][34][35] to determine whether graft-infiltrating Tregs are of thymic origin or peripherally induced in the graft. While the data suggest that the majority of graft-infiltrating Tregs show coexpression of these markers and are therefore considered as thymus derived, recent reports call the status of Helios and Nrp1 into question (36). Helios expression was reported to reflect recent TCR stimulation in addition to thymic origin (37), and Nrp1 was shown to be lacking on a proportion of thymic Tregs (38).…”

Section: Discussionmentioning

confidence: 99%