scholarly journals Coexpression of Helios in Foxp3+ Regulatory T Cells and Its Role in Human Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Wen-qing Yu ◽  
Ning-fei Ji ◽  
Cheng-jing Gu ◽  
Yan-li Wang ◽  
Mao Huang ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Regulatory T Cells ◽  
Solid Organ Transplantation ◽  
Connective Tissue Diseases ◽  
Foxp3 Expression ◽  
Solid Organ ◽  
Ample Evidence ◽  
Human Disorders ◽  
Lineage Stability

Regulatory T cells (Tregs) expressing the Foxp3 transcription factor are indispensable for the maintenance of immune system homeostasis. Tregs may lose Foxp3 expression or be reprogrammed into cells that produce proinflammatory cytokines, for example, Th1-like Tregs, Th2-like Tregs, Th17-like Tregs, and Tfh-like Tregs. Accordingly, selective therapeutic molecules that manipulate Treg lineage stability and/or functional activity might have the potential to improve aberrant immune responses in human disorders. In particular, the transcription factor Helios has emerged as an important marker and modulator of Tregs. Therefore, the current review focuses on recent findings on the expression, function, and mechanisms of Helios, as well as the patterns of Foxp3+ Tregs coexpressing Helios in various human disorders, in order to explore the potential of Helios for the improvement of many immune-related diseases. The studies were selected from PubMed using the library of the Nanjing Medical University in this review. The findings of the included studies indicate that Helios expression stabilizes the phenotype and function of Foxp3+ Tregs in certain inflammatory environments. Further, Tregs coexpressing Helios and Foxp3 were identified as a specific phenotype of stronger suppressor immune cells in both humans and animal models. Importantly, there is ample evidence that Helios-expressing Foxp3+ Tregs are relevant to various human disorders, including connective tissue diseases, infectious diseases, solid organ transplantation-related immunity, and cancer. Thus, Helios+Foxp3+CD4+ Tregs could be a valuable target in human diseases, and their potential should be explored further in the clinical setting.

Low-dose of tacrolimus favors the induction of functional CD4+CD25+FoxP3+ regulatory T cells in solid-organ transplantation

2009 ◽  
Vol 9 (5) ◽  
pp. 564-569 ◽  
Author(s):  
Zhen Wang ◽  
Bingyi Shi ◽  
Hailong Jin ◽  
Li Xiao ◽  
Yongwei Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Organ Transplantation ◽  
Low Dose ◽  
Solid Organ Transplantation ◽  
Solid Organ

scholarly journals Control of Germinal Center Localization and Lineage Stability of Follicular Regulatory T Cells by the Blimp1 Transcription Factor

Cell Reports ◽  
2019 ◽  
Vol 29 (7) ◽  
pp. 1848-1861.e6 ◽  
Author(s):  
Erxia Shen ◽  
Hardis Rabe ◽  
Lin Luo ◽  
Lei Wang ◽  
Qin Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Regulatory T Cells ◽  
Germinal Center ◽  
Lineage Stability

scholarly journals Regulatory T Cells and Kidney Transplantation

2018 ◽  
Vol 13 (11) ◽  
pp. 1760-1764 ◽  
Author(s):  
Paloma Leticia Martin-Moreno ◽  
Sudipta Tripathi ◽  
Anil Chandraker
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Organ Transplantation ◽  
Tissue Repair ◽  
Solid Organ Transplantation ◽  
Immunosuppressive Drugs ◽  
Solid Organ ◽  
Effective Expansion ◽  
Conventional Immunosuppression

The ability of the immune system to differentiate self from nonself is critical in determining the immune response to antigens expressed on transplanted tissue. Even with conventional immunosuppression, acceptance of the allograft is an active process often determined by the presence of regulatory T cells (Tregs). Tregs classically are CD4+ cells that constitutively express high levels of the IL-2 receptor α chain CD25, along with the transcription factor Foxp3. The use of Tregs in the field of solid organ transplantation is related specifically to the objective of achieving tolerance, with the goal of reducing or eliminating immunosuppressive drugs as well as maintaining tissue repair and managing acute rejection. A key issue in clinical use of Tregs is how to effectively expand the number of Tregs, either through increasing numbers of endogenous Tregs or by the direct infusion of exogenously expanded Tregs. In order to realize the benefits of Treg therapy in solid organ transplantation, a number of outstanding challenges need to be overcome, including assuring an effective expansion of Tregs, improving long-term Treg stability and reduction of risk-related to off-target, nonspecific, immunosuppressive effects related specially to cancer.

scholarly journals Control of Germinal Center Localization and Lineage Stability of Follicular Regulatory T Cells by the Blimp1 Transcription Factor

Cell Reports ◽  
2020 ◽  
Vol 31 (4) ◽  
pp. 107575
Author(s):  
Erxia Shen ◽  
Hardis Rabe ◽  
Lin Luo ◽  
Lei Wang ◽  
Qin Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Regulatory T Cells ◽  
Germinal Center ◽  
Lineage Stability

scholarly journals LFA-1 blockade induces effector and regulatory T-cell enrichment in lymph nodes and synergizes with CTLA-4Ig to inhibit effector function

Blood ◽  
2011 ◽  
Vol 118 (22) ◽  
pp. 5851-5861 ◽  
Author(s):  
Natalie M. Reisman ◽  
Tamara L. Floyd ◽  
Maylene E. Wagener ◽  
Allan D. Kirk ◽  
Christian P. Larsen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Therapeutic Potential ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Relative Distribution ◽  
Lymphocyte Function ◽  
Peripheral Lymph

Abstract Despite encouraging results using lymphocyte function antigen-1 (LFA-1) blockade to inhibit BM and solid organ transplantation rejection in nonhuman primates and humans, the precise mechanisms underlying its therapeutic potential are still poorly understood. Using a fully allogeneic murine transplantation model, we assessed the relative distribution of total lymphocyte subsets in untreated versus anti–LFA-1–treated animals. Our results demonstrated a striking loss of naive T cells from peripheral lymph nodes, a concomitant gain in blood after LFA-1 blockade, and a shift in phenotype of the cells remaining in the node to a CD62LloCD44hi profile. We determined that this change was due to a specific enrichment of activated, graft-specific effectors in the peripheral lymph nodes of anti–LFA-1–treated mice compared with untreated controls, and not to a direct effect of anti–LFA-1 on CD62L expression. LFA-1 blockade also resulted in a dramatic increase in the frequency of CD4+ FoxP3+ regulatory T cells in graft-draining nodes. Our results suggest that the differential impact of LFA-1 blockade on the distribution of naive versus effector and regulatory T cells may underlie its ability to inhibit alloreactive T-cell responses after transplantation.

scholarly journals Regulatory T cells: tolerance induction in solid organ transplantation

2017 ◽  
Vol 189 (2) ◽  
pp. 197-210 ◽  
Author(s):  
T. Vaikunthanathan ◽  
N. Safinia ◽  
D. Boardman ◽  
R. I. Lechler ◽  
G. Lombardi
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Tolerance Induction ◽  
Solid Organ

Donor-specific regulatory T cells might be used to induce tolerance in solid organ transplantation

2008 ◽  
Vol 71 (4) ◽  
pp. 602-604
Author(s):  
Yuchuan Huang ◽  
Jinjing Wang ◽  
Chuntao Zhang ◽  
Jun Shan ◽  
Shujuan Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Solid Organ

scholarly journals Basiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jacobo López-Abente ◽  
Marta Martínez-Bonet ◽  
Esther Bernaldo-de-Quirós ◽  
Manuela Camino ◽  
Nuria Gil ◽  
...  
Keyword(s):  
T Cells ◽  
Heart Transplant ◽  
Solid Organ Transplantation ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Protective Role ◽  
Regulatory Function ◽  
Solid Organ

AbstractCD25, the alpha chain of the IL-2 receptor, is expressed on activated effector T cells that mediate immune graft damage. Induction immunosuppression is commonly used in solid organ transplantation and can include antibodies blocking CD25. However, regulatory T cells (Tregs) also rely on CD25 for their proliferation, survival, and regulatory function. Therefore, CD25-blockade may compromise Treg protective role against rejection. We analysed in vitro the effect of basiliximab (BXM) on the viability, phenotype, proliferation and cytokine production of Treg cells. We also evaluated in vivo the effect of BXM on Treg in thymectomized heart transplant children receiving BXM in comparison to patients not receiving induction therapy. Our results show that BXM reduces Treg counts and function in vitro by affecting their proliferation, Foxp3 expression, and IL-10 secretion capacity. In pediatric heart-transplant patients, we observed decreased Treg counts and a diminished Treg/Teff ratio in BXM-treated patients up to 6-month after treatment, recovering baseline values at the end of the 12-month follow up period. These results reveal that the use of BXM could produce detrimental effects on Tregs, and support the evidence suggesting that BXM induction could impair the protective role of Tregs in the period of highest incidence of acute graft rejection.

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