scholarly journals Regulatory T Cells Exhibit Interleukin-33-Dependent Migratory Behavior during Skin Barrier Disruption

2021 ◽  
Vol 22 (14) ◽  
pp. 7443
Author(s):  
Sumika Toyama ◽  
Catharina Sagita Moniaga ◽  
Susumu Nakae ◽  
Masaru Kurosawa ◽  
Hideoki Ogawa ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Transforming Growth Factor ◽  
Sodium Dodecyl ◽  
Skin Barrier ◽  
Neutralizing Antibody ◽  
Interleukin 33 ◽  
Barrier Disruption ◽  
Inflammatory Conditions ◽  
Skin Infiltration

Regulatory T cells (Tregs) suppress immune responses and maintain immunological self-tolerance and homeostasis. We currently investigated relationships between skin barrier condition and Treg behavior using skin barrier-disrupted mice. Skin barrier disruption was induced by repeated topical application of 4% sodium dodecyl sulfate (SDS) on mice. The number of CD4+ forkhead box protein P3 (Foxp3)+ Tregs was higher in 4% SDS-treated skins than in controls. This increasing was correlated with the degree of acanthosis. The numbers of interleukin (IL)-10+ and transforming growth factor (TGF)-β+ Tregs also increased in 4% SDS-treated skins. Localization of IL-33 in keratinocytes shifted from nucleus to cytoplasm after skin barrier disruption. Notably, IL-33 promoted the migration of Tregs in chemotaxis assay. The skin infiltration of Tregs was cancelled in IL-33 neutralizing antibody-treated mice and IL-33 knockout mice. Thus, keratinocyte-derived IL-33 may induce Treg migration into barrier-disrupted skin to control the phase transition between healthy and inflammatory conditions.

scholarly journals Regulatory T-Cells Protect From Type 1 Diabetes After Induction by Coxsackievirus Infection in the Context of Transforming Growth Factor- 

Diabetes ◽  
2008 ◽  
Vol 57 (5) ◽  
pp. 1302-1311 ◽  
Author(s):  
M. J. Richer ◽  
N. Straka ◽  
D. Fang ◽  
I. Shanina ◽  
M. S. Horwitz
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Growth Factor ◽  
Regulatory T Cells ◽  
Transforming Growth Factor

scholarly journals Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice

2011 ◽  
Vol 208 (12) ◽  
pp. 2489-2496 ◽  
Author(s):  
Uri Sela ◽  
Peter Olds ◽  
Andrew Park ◽  
Sarah J. Schlesinger ◽  
Ralph M. Steinman
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Graft Versus Host Disease ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Spleen Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Naturally Occurring

Foxp3+ regulatory T cells (T reg cells) effectively suppress immunity, but it is not determined if antigen-induced T reg cells (iT reg cells) are able to persist under conditions of inflammation and to stably express the transcription factor Foxp3. We used spleen cells to stimulate the mixed leukocyte reaction (MLR) in the presence of transforming growth factor β (TGF-β) and retinoic acid. We found that the CD11chigh dendritic cell fraction was the most potent at inducing high numbers of alloreactive Foxp3+ cells. The induced CD4+CD25+Foxp3+ cells appeared after extensive proliferation. When purified from the MLR, iT reg cells suppressed both primary and secondary MLR in vitro in an antigen-specific manner. After transfer into allogeneic mice, iT reg cells persisted for 6 mo and prevented graft versus host disease (GVHD) caused by co-transferred CD45RBhi T cells. Similar findings were made when iT reg cells were transferred after onset of GVHD. The CNS2 intronic sequence of the Foxp3 gene in the persisting iT reg cells was as demethylated as the corresponding sequence of naturally occurring T reg cells. These results indicate that induced Foxp3+ T reg cells, after proliferating and differentiating into antigen-specific suppressive T cells, can persist for long periods while suppressing a powerful inflammatory disease.

CD28 disruption exacerbates inflammation in Tgf-β1-/- mice: in vivo suppression by CD4+CD25+ regulatory T cells independent of autocrine TGF-β1

Blood ◽  
2004 ◽  
Vol 103 (12) ◽  
pp. 4594-4601 ◽  
Author(s):  
Mizuko Mamura ◽  
WoonKyu Lee ◽  
Timothy J. Sullivan ◽  
Angelina Felici ◽  
Anastasia L. Sowers ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Transforming Growth Factor ◽  
Cytotoxic T Lymphocyte ◽  
Tumor Necrosis Factor Receptor ◽  
Transforming Growth Factor Β1 ◽  
Autoimmune Inflammatory Disease ◽  
Lymph Node Cells ◽  
Tgf Β1

Abstract Tgf-β1-/- mice develop a progressive, lethal, inflammatory syndrome, but mechanisms leading to the spontaneous activation of Tgf-β1-/- T cells remain unclear. Here we show the disruption of CD28 gene expression accelerates disease in Tgf-β1-/- mice, and we link this increase in severity to a reduction in the number of CD4+CD25+ regulatory T cells. CD4+CD25+ T cells develop normally in Tgf-β1-/- mice and display characteristic expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor (GITR), αEβ7 integrin, and Foxp3. Adoptive transfer of Tgf-β1-/- splenocytes to Tgf-β1+/+/Rag2-/- mice induced an autoimmune inflammatory disease with features similar to those of the Tgf-β1-/- phenotype, and disease transfer was accelerated by the depletion of Tgf-β1-/- CD4+CD25+ T cells from donor splenocytes. Cotransfer of Tgf- β1-/- CD4+CD25+ T cells clearly attenuated disease in Rag2-/- recipients of CD25+-depleted Tgf-β1-/- spleen and lymph node cells, but suppression was incomplete when compared with Tgf-β1+/+ CD4+CD25+ T cells. These data demonstrate that CD4+CD25+ regulatory T cells develop in complete absence of endogenous transforming growth factor-β1 (TGF-β1) expression and that autocrine TGF-β1 expression is not essential for these cells to suppress inflammation in vivo. (Blood. 2004;103:4594-4601)

scholarly journals Transforming Growth Factor-β Signaling in Regulatory T Cells Controls T Helper-17 Cells and Tissue-Specific Immune Responses

Immunity ◽  
2017 ◽  
Vol 46 (4) ◽  
pp. 660-674 ◽  
Author(s):  
Joanne E. Konkel ◽  
Dunfang Zhang ◽  
Peter Zanvit ◽  
Cheryl Chia ◽  
Tamsin Zangarle-Murray ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
T Helper ◽  
T Helper 17 ◽  
T Helper 17 Cells ◽  
Tissue Specific

Naturally occurring regulatory T cells show reduced sensitivity toward oxidative stress–induced cell death

Blood ◽  
2009 ◽  
Vol 113 (15) ◽  
pp. 3542-3545 ◽  
Author(s):  
Dimitrios Mougiakakos ◽  
C. Christian Johansson ◽  
Rolf Kiessling
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Cell Death ◽  
Regulatory T Cells ◽  
Suppressor Cells ◽  
Underlying Mechanism ◽  
Myeloid Derived Suppressor Cells ◽  
Inflammatory Conditions ◽  
Naturally Occurring ◽  
Solid Malignancies

Abstract Although the authors of several studies report elevated numbers of immunosuppressive regulatory T cells (Tregs) in hematologic and solid malignancies, the underlying mechanism is not fully clarified. Cancer is associated with oxidative stress mediated through reactive oxygen species produced by malignant cells, granulocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. Oxidative stress is known to have detrimental effects on natural killer (NK) and T cells during chronic inflammatory conditions and cancer. Paradoxically, greater numbers of Tregs can be detected at tumor sites, indicating that Tregs can persist in this environment of increased oxidative stress. We demonstrate that Tregs, especially naive CD45RA+, exhibit reduced sensitivity to oxidative stress–induced cell death and maintain their suppressive function, a phenomenon that may be attributed to their observed high antioxidative capacity. This newly described characteristic could explain their enrichment in malignancies associated with increased levels of oxidative stress.

Leflunomide induces immunosuppression in collagen-induced arthritis rats by upregulating CD4+CD25+ regulatory T cells

2010 ◽  
Vol 88 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Ting-Yu Wang ◽  
Jun Li ◽  
Chang-Yu Li ◽  
Yong Jin ◽  
Xiong-Wen Lü ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Regulatory T Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Con A ◽  
Collagen Induced Arthritis ◽  
Foxp3 Mrna ◽  
Tgf Β1

This study was to investigate the effect of leflunomide on the immunosuppressive CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) in collagen-induced arthritis (CIA) rats. CIA was induced by collagen type II in Wistar rats. Immunofluorescence flow cytometry and RT-PCR were used to determine the proportion of CD4+CD25+ Tregs and the expression of Foxp3 mRNA, respectively. Proliferation of T lymphocytes was assayed with MTT reagent, and the level of transforming growth factor β1 (TGF-β1) in the supernatant of concanavalin A (Con A)-induced T lymphocytes was determined by ELISA kit. Our investigations demonstrated that inhibition of arthritis by leflunomide was related to changes in CD4+CD25+ Tregs. In addition, A771726, which is the active metabolite of leflunomide, promoted the differentiation of spleen lymphocytes into CD4+CD25+ Tregs, increased antiinflammatory cytokine TGF-β1 secretion, and adjusted the activity of Con A-induced lymphocytes in vitro.

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