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Regulatory T cell-mediated anti-inflammatory effects promote successful tissue repair in both indirect and direct manners.

Lei H, Schmidt-Bleek K, Dienelt A, Reinke P, Volk HD - Front Pharmacol (2015)

Bottom Line: We describe tissue-resident Treg and their specific phenotypes in skin, visceral adipose tissue, and skeletal muscle.We hypothesize a cross-talk between Treg and bone-forming cells through the CD39-CD73-(adenosine)-adenosine receptor pathway, which might also potentiate the differentiation of MSCs, thus facilitating bone regeneration.This hypothesis may provide a road map for further investigations on the cross-talk between the immune and the skeletal system, and also enable the development of better strategies to promote bone repair and regeneration.

View Article: PubMed Central - PubMed

Affiliation: Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine Berlin , Berlin, Germany ; Institute for Medical Immunology, Charité University Medicine Berlin , Berlin, Germany.

ABSTRACT
Regulatory T cells (Tregs) offer new immunotherapeutic options to control undesired immune reactions, such as those in transplant rejection and autoimmunity. In addition, tissue repair and regeneration depend on a multitude of tightly regulated immune and non-immune cells and signaling molecules. There is mounting evidence that adequate innate responses, and even more importantly balanced adaptive immune responses, are key players in the tissue repair and regeneration processes, even in absence of any immune-related disease or infection. Thus, the anti-inflammatory and anti-apoptotic capacities of Treg can affect not only the effector immune response, creating the appropriate immune environment for successful tissue repair and regeneration, but growing evidence shows that they also have direct effects on tissue cell functions. Here we summarize the present views on how Treg might support tissue regeneration by direct control of undesired immune reactivity and also by direct interaction with non-immune tissue cells. We describe tissue-resident Treg and their specific phenotypes in skin, visceral adipose tissue, and skeletal muscle. In addition, we touch on the topic of osteoimmunology, discussing the direct interactions of Treg with bone-forming cells, such as osteoblasts and their mesenchymal stromal cell (MSC) progenitors-a field which is under-investigated. We hypothesize a cross-talk between Treg and bone-forming cells through the CD39-CD73-(adenosine)-adenosine receptor pathway, which might also potentiate the differentiation of MSCs, thus facilitating bone regeneration. This hypothesis may provide a road map for further investigations on the cross-talk between the immune and the skeletal system, and also enable the development of better strategies to promote bone repair and regeneration.

No MeSH data available.


Related in: MedlinePlus

A proportion of Treg express an effector-memory phenotype in healthy donors. (A) Proportions of Treg subsets in total Treg in healthy donors (mean ± SD, n = 36, age 19–87 years). (B) A significant proportion of expanded naïve (TregN) and central-memory Treg (TregCM) converted into EM (CD45RA–CD62L–) phenotype upon 3 weeks of expansion with poly-clonal stimulation in the presence of rapamycin and interleukin 2. The mean frequency of cells expressing an EM phenotype is indicated for each cell type before and after expansion. (n = 5), paired t-test, taken from Lei et al. (2015) **p < 0.01.
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Figure 2: A proportion of Treg express an effector-memory phenotype in healthy donors. (A) Proportions of Treg subsets in total Treg in healthy donors (mean ± SD, n = 36, age 19–87 years). (B) A significant proportion of expanded naïve (TregN) and central-memory Treg (TregCM) converted into EM (CD45RA–CD62L–) phenotype upon 3 weeks of expansion with poly-clonal stimulation in the presence of rapamycin and interleukin 2. The mean frequency of cells expressing an EM phenotype is indicated for each cell type before and after expansion. (n = 5), paired t-test, taken from Lei et al. (2015) **p < 0.01.

Mentions: Expression of chemokine receptors on Treg, like CCR6, CXCR3, CCR4, CCR7, and CCR10 that support attraction of Treg to the specific tissues and execute rapid intra-tissue regulation (Grindebacke et al., 2009; Duhen et al., 2012; Chow et al., 2015). We recently demonstrated that about 10% Treg in the peripheral blood of healthy donors and patients awaiting for kidney transplantation express an effector-memory phenotype (CD45RA–CD62L–) allowing migration into inflamed tissues without further activation (Figure 2A). Upon in vitro expansion, a significant proportion of both naïve (CD45RA+CD62L+) and central-memory (CD45RA–CD62L+) Treg shift their phenotype into effector-memory like (Figure 2B), which could facilitate further migration of Treg into tissues when the expanded Treg products are transferred into patients (Lei et al., 2015).


Regulatory T cell-mediated anti-inflammatory effects promote successful tissue repair in both indirect and direct manners.

Lei H, Schmidt-Bleek K, Dienelt A, Reinke P, Volk HD - Front Pharmacol (2015)

A proportion of Treg express an effector-memory phenotype in healthy donors. (A) Proportions of Treg subsets in total Treg in healthy donors (mean ± SD, n = 36, age 19–87 years). (B) A significant proportion of expanded naïve (TregN) and central-memory Treg (TregCM) converted into EM (CD45RA–CD62L–) phenotype upon 3 weeks of expansion with poly-clonal stimulation in the presence of rapamycin and interleukin 2. The mean frequency of cells expressing an EM phenotype is indicated for each cell type before and after expansion. (n = 5), paired t-test, taken from Lei et al. (2015) **p < 0.01.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4557110&req=5

Figure 2: A proportion of Treg express an effector-memory phenotype in healthy donors. (A) Proportions of Treg subsets in total Treg in healthy donors (mean ± SD, n = 36, age 19–87 years). (B) A significant proportion of expanded naïve (TregN) and central-memory Treg (TregCM) converted into EM (CD45RA–CD62L–) phenotype upon 3 weeks of expansion with poly-clonal stimulation in the presence of rapamycin and interleukin 2. The mean frequency of cells expressing an EM phenotype is indicated for each cell type before and after expansion. (n = 5), paired t-test, taken from Lei et al. (2015) **p < 0.01.
Mentions: Expression of chemokine receptors on Treg, like CCR6, CXCR3, CCR4, CCR7, and CCR10 that support attraction of Treg to the specific tissues and execute rapid intra-tissue regulation (Grindebacke et al., 2009; Duhen et al., 2012; Chow et al., 2015). We recently demonstrated that about 10% Treg in the peripheral blood of healthy donors and patients awaiting for kidney transplantation express an effector-memory phenotype (CD45RA–CD62L–) allowing migration into inflamed tissues without further activation (Figure 2A). Upon in vitro expansion, a significant proportion of both naïve (CD45RA+CD62L+) and central-memory (CD45RA–CD62L+) Treg shift their phenotype into effector-memory like (Figure 2B), which could facilitate further migration of Treg into tissues when the expanded Treg products are transferred into patients (Lei et al., 2015).

Bottom Line: We describe tissue-resident Treg and their specific phenotypes in skin, visceral adipose tissue, and skeletal muscle.We hypothesize a cross-talk between Treg and bone-forming cells through the CD39-CD73-(adenosine)-adenosine receptor pathway, which might also potentiate the differentiation of MSCs, thus facilitating bone regeneration.This hypothesis may provide a road map for further investigations on the cross-talk between the immune and the skeletal system, and also enable the development of better strategies to promote bone repair and regeneration.

View Article: PubMed Central - PubMed

Affiliation: Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine Berlin , Berlin, Germany ; Institute for Medical Immunology, Charité University Medicine Berlin , Berlin, Germany.

ABSTRACT
Regulatory T cells (Tregs) offer new immunotherapeutic options to control undesired immune reactions, such as those in transplant rejection and autoimmunity. In addition, tissue repair and regeneration depend on a multitude of tightly regulated immune and non-immune cells and signaling molecules. There is mounting evidence that adequate innate responses, and even more importantly balanced adaptive immune responses, are key players in the tissue repair and regeneration processes, even in absence of any immune-related disease or infection. Thus, the anti-inflammatory and anti-apoptotic capacities of Treg can affect not only the effector immune response, creating the appropriate immune environment for successful tissue repair and regeneration, but growing evidence shows that they also have direct effects on tissue cell functions. Here we summarize the present views on how Treg might support tissue regeneration by direct control of undesired immune reactivity and also by direct interaction with non-immune tissue cells. We describe tissue-resident Treg and their specific phenotypes in skin, visceral adipose tissue, and skeletal muscle. In addition, we touch on the topic of osteoimmunology, discussing the direct interactions of Treg with bone-forming cells, such as osteoblasts and their mesenchymal stromal cell (MSC) progenitors-a field which is under-investigated. We hypothesize a cross-talk between Treg and bone-forming cells through the CD39-CD73-(adenosine)-adenosine receptor pathway, which might also potentiate the differentiation of MSCs, thus facilitating bone regeneration. This hypothesis may provide a road map for further investigations on the cross-talk between the immune and the skeletal system, and also enable the development of better strategies to promote bone repair and regeneration.

No MeSH data available.


Related in: MedlinePlus