FoxP3+RORγt+ T Helper Intermediates Display Suppressive Function against Autoimmune Diabetes

Tartar, Danielle; VanMorlan, Amie M.; Wan, Xiaoxiao; Güloğlu, F. Betül; Jain, Renu; Haymaker, Cara; Ellis, Jason S.; Hoeman, Christine; Cascio, Jason A.; Dhakal, Mermagya; Oukka, Mohamed; Zaghouani, Habib

doi:10.4049/jimmunol.0903324

Cited by 73 publications

(68 citation statements)

References 46 publications

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“…+ RORgt + T cells in the absence of cognate TCR Ag RORgt + T cells also include a significant proportion of Foxp3 + cells that express IL-10 and CCL20 (2), shown recently to regulate effector cells in the pancreas of diabetes-prone NOD mice (15). However, no Foxp3 + RORgt + T cells were generated in RAGdeficient Marilyn mice (Fig.…”

Section: Lack Of Foxp3mentioning

confidence: 97%

“…Nevertheless, RORgt + T cells include both IL-17 + proinflammatory cells and Foxp3 + regulatory cells, at a ratio that is characteristic of a given tissue and remains stable during acute infection and inflammation (2). It has been shown recently that Foxp3 + RORgt + T cells migrate to sites of inflammation and protect against diabetes in NOD mice (15). More generally, Wohlfert and Belkaid (16) have discussed the idea that subsets of regulatory T cells (Tregs) express transcription factors associated with effector T cell lineages to adapt regulation to specific inflammatory settings.…”

Section: S Ubsets Of Tcrabmentioning

confidence: 99%

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Restricted Microbiota and Absence of Cognate TCR Antigen Leads to an Unbalanced Generation of Th17 Cells

Lochner

Bérard

Sawa

et al. 2011

The Journal of Immunology

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Retinoic acid-related orphan receptor (ROR)γt+ TCRαβ+ cells expressing IL-17, termed Th17 cells, are most abundant in the intestinal lamina propria. Symbiotic microbiota are required for the generation of Th17 cells, but the requirement for microbiota-derived Ag is not documented. In this study, we show that normal numbers of Th17 cells develop in the intestine of mice that express a single TCR in the absence of cognate Ag, whereas the microbiota remains essential for their development. However, such mice, or mice monocolonized with the Th17-inducing segmented filamentous bacteria, fail to induce normal numbers of Foxp3+ RORγt+ T cells, the regulatory counterpart of IL-17+RORγt+ T cells. These results demonstrate that a complex microbiota and cognate Ag are required to generate a properly regulated set of RORγt+ T cells and Th17 cells.

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Section: Lack Of Foxp3mentioning

confidence: 97%

Section: S Ubsets Of Tcrabmentioning

confidence: 99%

Restricted Microbiota and Absence of Cognate TCR Antigen Leads to an Unbalanced Generation of Th17 Cells

Lochner

Bérard

Sawa

et al. 2011

The Journal of Immunology

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“…To our knowledge, our study is the first to compare Treg cells in a large cohort of newonset T1D using a highly specific FOXP3 int T cells that express the Th17 lineage transcription factor RORgt arise before islet inflammation, and they may differentiate in vitro to either Th17 or Tregs (24). The elevated population of IL-17-secreting CD45RA 2…”

Section: Foxp3mentioning

confidence: 99%

Cutting Edge: Increased IL-17–Secreting T Cells in Children with New-Onset Type 1 Diabetes

Marwaha

Crome

Panagiotopoulos

et al. 2010

The Journal of Immunology

187

142

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“…It was later determined, however, that the membranebound TGF-b-bearing Tregs express both FoxP3 (at intermediate levels) and RORgt, and these FoxP3 int RORgt + utilize CD62L to migrate from the spleen to the pancreas during insulitis and are no longer expandable in the inflammatory location [72]. Interestingly, these Tregs did not develop in the thymus and were able to convert into IL-17 producers upon polarization [72]. Therefore, the suppressors may represent peripheral transitional intermediates.…”

Section: Mechanisms Of Antigen-specific Tolerancementioning

confidence: 98%

Antigen-Specific Therapy Against Type 1 Diabetes: Mechanisms and Perspectives

Wan

Zaghouani

2014

Immunotherapy

Self Cite

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Type 1 diabetes (T1D) is an immune-mediated disease that occurs when the insulin-producing β‑cells of the pancreatic islets are destroyed by an inflammatory process perpetuated by cells of the immune system. The logical approach to suppress T1D is to inactivate or eliminate the lymphocytes responsible for inducing inflammation and targeting the β‑cells. Antigen-specific approaches have been devised and were able to target inflammatory lymphocytes and induce apoptosis or block trafficking to pancreatic islets. Lack of costimulation, expansion of Tregs and bystander suppression are likely mechanisms by which antigen-specific treatments modulate pathogenic T cells. This strategy, however, while prevents the onset of T1D, could not overcome overt T1D, perhaps because of collateral damage to the islet vascular network. Recent developments indicate that donor endothelial stem cell precursors can repair the islets' vascular niche and assist antigen-specific therapy against overt T1D.

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FoxP3+RORγt+ T Helper Intermediates Display Suppressive Function against Autoimmune Diabetes

Abstract: Material Supplementary 4.DC1http://www.jimmunol.org/content/suppl/2010/02/22/jimmunol.090332

Cited by 73 publications

References 46 publications

Restricted Microbiota and Absence of Cognate TCR Antigen Leads to an Unbalanced Generation of Th17 Cells

Restricted Microbiota and Absence of Cognate TCR Antigen Leads to an Unbalanced Generation of Th17 Cells

Cutting Edge: Increased IL-17–Secreting T Cells in Children with New-Onset Type 1 Diabetes

Antigen-Specific Therapy Against Type 1 Diabetes: Mechanisms and Perspectives

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