TIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity

Riquelme, Paloma; Haarer, Jan; Kammler, Anja; Walter, Lisa; Tomiuk, Stefan; Ahrens, Norbert; Wege, Anja K.; Goecze, Ivan; Zecher, Daniel; Banas, Bernhard; Spang, Rainer; Fändrich, F.; Lutz, Manfred B.; Sawitzki, Birgit; Schlitt, Hans J.; Ochando, Jordi; Geissler, Edward K.; Hutchinson, James A.

doi:10.1038/s41467-018-05167-8

Cited by 104 publications

(103 citation statements)

References 73 publications

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“…[53][54][55][56] Mreg macrophages respond to the stimulation of Treg cells and are responsible for inducing the repair response and inhibiting triggering of mechanisms that produce pro-inflammatory cytokines in tissue lesions. [57][58][59] Mox macrophages differ from the other cell types in expressing oxidized 1palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine and producing HO-1 and sulfiredoxin-1. [60][61][62] Mox macrophages are also associated with triggering of oxidative responses (Table 1).…”

Section: Macrophage Phenotypesmentioning

confidence: 99%

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Sousa¹,

Vasconcelos²,

Quaresma³

2019

IDR

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Macrophages are a functionally heterogeneous group of cells with specialized functions depending not only on their subgroup but also on the function of the organ or tissue in which the cells are located. The concept of macrophage phenotypic heterogeneity has been investigated since the 1980s, and more recent studies have identified a diverse spectrum of phenotypic subpopulations. Several types of macrophages play a central role in the response to infectious agents and, along with other components of the immune system, determine the clinical outcome of major infectious diseases. Here, we review the functions of various macrophage phenotypic subpopulations, the concept of macrophage polarization, and the influence of these cells on the evolution of infections. In addition, we emphasize their role in the immune response in vivo and in situ, as well as the molecular effectors and signaling mechanisms used by these cells. Furthermore, we highlight the mechanisms of immune evasion triggered by infectious agents to counter the actions of macrophages and their consequences. Our aim here is to provide an overview of the role of macrophages in the pathogenesis of critical transmissible diseases and discuss how elucidation of this relationship could enhance our understanding of the host–pathogen association in organ-specific immune responses.

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Section: Macrophage Phenotypesmentioning

confidence: 99%

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Sousa¹,

Vasconcelos²,

Quaresma³

2019

IDR

View full text Add to dashboard Cite

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“…anergy induction, infectious tolerance, bystander suppression) cannot be excluded. [75][76][77] Nevertheless, these data suggest this co-cultured cell product was more potent towards donorspecific antigens than third-party cells. The underlying mechanisms of operational tolerance induced by this cell therapy are yet undiscovered.…”

Section: Livermentioning

confidence: 88%

“…via regulatory dendritic cells or macrophages) or multi‐cellular immunoregulation (e.g. anergy induction, infectious tolerance, bystander suppression) cannot be excluded . Nevertheless, these data suggest this co‐cultured cell product was more potent towards donor‐specific antigens than third‐party cells.…”

Section: Clinical Trials: Today and Tomorrowmentioning

confidence: 91%

Regulatory T cells in solid organ transplantation

et al. 2020

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The induction of graft tolerance remains the holy grail of transplantation. This is important as chronic allograft dysfunction and the side effects of immunosuppression regimens place a major burden on the lives of transplant patients and their healthcare systems. This has mandated the need to understand the immunobiology of graft rejection and identify novel therapeutics. Regulatory T (Treg) cells play an important role in modulating pro‐inflammatory microenvironments and maintaining tissue homeostasis. However, there are fundamental unanswered questions regarding Treg cell immunobiology. These cells are a heterogeneous entity with functionally diverse roles. Moreover, the adoption of novel deeper immunophenotyping and genomic sequencing technologies has identified this phenotype and function to be more complex than expected. Hence, a comprehensive understanding of Treg cell heterogeneity is needed to safely and effectively exploit their therapeutic potential. From a clinical perspective, the recent decade has seen different clinical teams commence and complete first‐in‐man clinical trials utilising Treg cells as an adoptive cellular therapy. In this review, we discuss these trials from a translational perspective with an important focus on safety. Finally, we identify crucial knowledge gaps for future study.

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“…In a heterotopic mouse heart transplant model, donor strain Mreg infusion prior to transplantation significantly prolongs allograft survival via IFN-γ induced IDO activity. 95 93 Similarly, human Mregs derived from in vitro culture have also been shown to exert potent inhibitory effects on alloimmune responses in an IDO-dependent manner.…”

Section: Regulatory Macrophagesmentioning

confidence: 99%

“…94 More recently, Hutchinson's group showed that human Mregs can convert allogeneic CD4 + T cells into IL-10-producing, TIGIT + Foxp3 + iTregs that exert bystander T cell suppression as well as inhibit DC maturation. 95 This ability is dependent on signals mediated by IDO, TGF-β, retinoic acid, Notch and the progestagen-associated endometrial protein. In a clinical study of living-donor kidney transplant recipients, preoperative administration of donor-derived Mregs resulted in an acute increase in circulating TIGIT + Tregs.…”

Section: Regulatory Macrophagesmentioning

confidence: 99%

Impact of infection on transplantation tolerance

Luo

2019

Immunological Reviews

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Allograft tolerance is the ultimate goal of organ transplantation. Current strategies for tolerance induction mainly focus on inhibiting alloreactive T cells while promoting regulatory immune cells. Pathogenic infections may have direct impact on both effector and regulatory cell populations, therefore can alter host susceptibility to transplantation tolerance induction as well as impair the quality and stability of tolerance once induced. In this review, we will discuss existing data demonstrating the effect of infections on transplantation tolerance, with particular emphasis on the role of the stage of infection (acute, chronic, or latent) and the stage of tolerance (induction or maintenance) in this infection‐tolerance interaction. While the deleterious effect of acute infection on tolerance is mainly driven by proinflammatory cytokines induced shortly after the infection, chronic infection may generate exhausted T cells that could in fact facilitate transplantation tolerance. In addition to pathogenic infections, commensal intestinal microbiota also has numerous significant immunomodulatory effects that can shape the host alloimmunity following transplantation. A comprehensive understanding of these mechanisms is crucial for the development of therapeutic strategies for robustly inducing and stably maintaining transplantation tolerance while preserving host anti‐pathogen immunity in clinically relevant scenarios.

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TIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity

Cited by 104 publications

References 73 publications

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Regulatory T cells in solid organ transplantation

Impact of infection on transplantation tolerance

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