Identification and characterization of latency-associated peptide-expressing γδ T cells

Rezende, Rafael M.; Cunha, André Pires da; Kuhn, Chantal; Rubino, Stephen; M’Hamdi, Hanane; Gabriely, Galina; Vandeventer, Tyler; Liu, Shirong; Cialic, Ron; Pinheiro-Rosa, Natália; Oliveira, Raquel Peres de; Gaublomme, Jellert T.; Obholzer, Nikolaus; Kozubek, James; Pochet, Nathalie; Faria, Ana Maria Caetano; Weiner, Howard L.

doi:10.1038/ncomms9726

Cited by 35 publications

(31 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In these cultures, presence of neutralizing antibodies for IL-10 and TGF-β abrogated the iTreg-induced suppression of IL-5 and IL-13 production by ILC2s (Fig 3, C ), confirming that suppression of ILC2s by iTregs is mediated by IL-10 and TGF-β. Some regulatory T cells express a form of membrane-bound TGF-β1 known as latency-associated peptide (LAP) (17). We asked if blocking ICOS:ICOS-L interaction could modulate the level of IL-10 expression or the percentage of LAP-expressing cells in co-cultures of iTregs and ILC2s.…”

Section: Resultsmentioning

confidence: 99%

Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator–inducible T-cell costimulator ligand interaction

Rigas

Lewis

Aron

et al. 2017

Journal of Allergy and Clinical Immunology

160

166

View full text Add to dashboard Cite

Background Atopic diseases including asthma exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T cells (Tregs) and the emerging group 2 innate lymphoid cells (ILC2s). While ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. Objective In the present study, we evaluate for the first time how Tregs interact with pulmonary ILC2s and control their function. Methods ILC2s and Tregs were evaluated using in vitro suppression assays, cell-contact assays, and gene expression panels. Also, human ILC2s and Tregs were adoptively transferred into NOD SCID gamma-C deficient (NSG) mice, which were given isotype or anti-ICOS-L antibodies, then challenged with IL-33 and assessed for AHR. Results We show that induced Tregs (iTregs), but not natural Tregs (nTregs), effectively suppress the production of ILC2-driven, pro-inflammatory cytokines IL-5 and IL-13, both in vitro and in vivo. Mechanistically, our data reveal the necessity of Inducible T cell Costimulator (ICOS):ICOS-Ligand cell contact for Treg-mediated ILC2 suppression, alongside suppressive cytokines TGF-β and IL-10. Using a translational approach, we then demonstrate that human iTregs suppress syngeneic human ILC2s via ICOS-L to control airway inflammation in a humanized ILC2 mouse model. Conclusion These findings suggest that peripheral expansion of induced Tregs may serve as a promising therapeutic target against ILC2-dependent asthma.

show abstract

Section: Resultsmentioning

confidence: 99%

Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator–inducible T-cell costimulator ligand interaction

Rigas

Lewis

Aron

et al. 2017

Journal of Allergy and Clinical Immunology

160

166

View full text Add to dashboard Cite

show abstract

“…In tumors, γδ T cells can display cytotoxic or regulatory functions. Regulatory γδ T cells can express latency‐associated peptide (LAP), which is converted to TGF‐β1 by thrombospondin‐1 (TSP‐1) …”

Section: γδ T Cellsmentioning

confidence: 99%

“…90 In contrast with prototypical Th17, to TGF-β1 by thrombospondin-1 (TSP-1). 136 Inmice,CD73isexpressedonmorethan90%ofperipheralγδ T cells. 137 CD73isexpressedinaTCR-ligandinduciblemannerandits expressionassociatedwithenrichmentoftranscriptionfactorslinked to effector function.…”

Section: Incontrasttothepro-inflammatoryeffectsofatpexpressionof Cd3mentioning

confidence: 99%

The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets

Allard

Longhi

Robson

et al. 2017

Immunological Reviews

716

610

View full text Add to dashboard Cite

Summary Cancers are able to grow by subverting immune suppressive pathways, to prevent the malignant cells as being recognized as dangerous or foreign. This mechanism prevents the cancer from being eliminated by the immune system and allows disease to progress from a very early stage to a lethal state. Immunotherapies are newly developing interventions that modify the patient’s immune system to fight cancer, by either directly stimulating rejection-type processes or by blocking suppressive pathways. Extracellular adenosine generated by the ectonucleotidases CD39 and CD73 is a newly recognized “immune checkpoint mediator” that interferes with anti-tumor immune responses. In this review, we focus on CD39 and CD73 ectoenzymes and encompass aspects of the biochemistry of these molecules as well as detailing the distribution and function on immune cells. Effects of CD39 and CD73 inhibition in preclinical and clinical studies are discussed. Finally, we provide insights into potential clinical application of adenosinergic and other purinergic-targeting therapies and forecast how these might develop in combination with other anti-cancer modalities.

show abstract

“…Rezende et al have described the migration of thymic γδ T cells to the periphery, where they upregulate membrane-bound TGF-β1 and acquire a regulatory phenotype (Rezende et al 2015). The regulatory function of such cells manifests via their ability to function as antigen presenting cells, which then induce classical CD4+ Foxp3+ regulatory T cells.…”

Section: γδ T Cells: Atypical Regulatory T Cellsmentioning

confidence: 99%

Lymphocyte-mediated Immune Regulation in Health and Disease: The Treg and γδ T Cell Co-conspiracy

Payne

2016

Immunological Investigations

View full text Add to dashboard Cite

The significance of lymphocytes functioning to mediate immunological tolerance has garnered increasing appreciation during the last several decades. CD4+ CD25+ α/β T cells have arguably been the most extensively studied regulatory lymphocyte to date, perhaps owing to the dramatic phenotype observed mice and humans with mutated Foxp3. However, emerging studies suggest that the lineage of regulatory lymphocytes is quite robust. Most notably, while γδ T cells are more traditionally regarded as mediators of cytotoxic function, they are beginning to be regarded as potential negative regulators of immunity. While regulatory γ/δ T cells may possess a degree of transcriptional overlap with ‘classical Tregs’, there remains less clarity in regards to the mechanisms driving the suppressive potential of these cells. In this review, I will discuss the role of Tregs in establishing tolerance in the steady state as well as disease, and how their accumulation and function may be modulated by myeloid cells in the local microenvironment. I will also discuss the necessity to extend our understanding of the regulatory nature of γδ T cells, which may lead to the unearthing of novel paradigms of immunity, perhaps most notably with respect to cancer.

show abstract

Identification and characterization of latency-associated peptide-expressing γδ T cells

Cited by 35 publications

References 56 publications

Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator–inducible T-cell costimulator ligand interaction

Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator–inducible T-cell costimulator ligand interaction

The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets

Lymphocyte-mediated Immune Regulation in Health and Disease: The Treg and γδ T Cell Co-conspiracy

Contact Info

Product

Resources

About