T H 17 cell plasticity: The role of dendritic cells and molecular mechanisms

Agalioti, Theodora; Villablanca, Eduardo J.; Huber, Samuel; Gagliani, Nicola

doi:10.1016/j.jaut.2017.12.003

Cited by 51 publications

(45 citation statements)

References 99 publications

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“…In the case of glaucoma, GvHD, and scleritis, we have seen the factors regulating the Th1 pathway, whereas Sjögren's syndrome is regulated by the Th2 pathway. On the other hand, there is involvement of Th17 pathways in the case of glaucoma, DED, scleritis, and Sjögren's syndrome and the Treg pathway in the case of scleritis [7,[66][67][68][69][70]. The reliability of these common mechanisms in different diseases can be compared with the mouse studies, which are beyond the capacity of this manuscript.…”

Section: Discussionmentioning

confidence: 99%

The Innate Immune Cell Profile of the Cornea Predicts the Onset of Ocular Surface Inflammatory Disorders

Palomar

Montolío

Cegoñino

et al. 2019

JCM

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Ocular surface inflammatory disorder (OSID) is a spectrum of disorders that have features of several etiologies whilst displaying similar phenotypic signs of ocular inflammation. They are complicated disorders with underlying mechanisms related to several autoimmune disorders, such as rheumatoid arthritis (RA), Sjögren’s syndrome, and systemic lupus erythematosus (SLE). Current literature shows the involvement of both innate and adaptive arms of the immune system in ocular surface inflammation. The ocular surface contains distinct components of the immune system in the conjunctiva and the cornea. The normal conjunctiva epithelium and sub-epithelial stroma contains resident immune cells, such as T cells, B cells (adaptive), dendritic cells, and macrophages (innate). The relative sterile environment of the cornea is achieved by the tolerogenic properties of dendritic cells in the conjunctiva, the presence of regulatory lymphocytes, and the existence of soluble immunosuppressive factors, such as the transforming growth factor (TGF)-β and macrophage migration inhibitory factors. With the presence of both innate and adaptive immune system components, it is intriguing to investigate the most important leukocyte population in the ocular surface, which is involved in immune surveillance. Our meta-analysis investigates into this with a focus on both infectious (contact lens wear, corneal graft rejection, Cytomegalovirus, keratitis, scleritis, ocular surgery) and non-infectious (dry eye disease, glaucoma, graft-vs-host disease, Sjögren’s syndrome) situations. We have found the predominance of dendritic cells in ocular surface diseases, along with the Th-related cytokines. Our goal is to improve the knowledge of immune cells in OSID and to open new dimensions in the field. The purpose of this study is not to limit ourselves in the ocular system, but to investigate the importance of dendritic cells in the disorders of other mucosal organs (e.g., lungs, gut, uterus). Holistically, we want to investigate if this is a common trend in the initiation of any disease related to the mucosal organs and find a unified therapeutic approach. In addition, we want to show the power of computational approaches to foster a collaboration between computational and biological science.

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Section: Discussionmentioning

confidence: 99%

The Innate Immune Cell Profile of the Cornea Predicts the Onset of Ocular Surface Inflammatory Disorders

Palomar

Montolío

Cegoñino

et al. 2019

JCM

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“…3B-D) and some other evidence suggest DCs directly modulate the heterogeneity and plasticity of Th17 cells ( 15 ). Whether DCs regulate Th17 responses through the expression of specialized regulators is still unclear ( 52 ). To identify such regulators, we focused on genes that would be uniquely expressed in ppTh17 but not in cdTh17 cells.…”

Section: Identification Of Caspase-1 As a Dc-induced T-cell-intrinsimentioning

confidence: 99%

Transcriptome profiling of pathogen-specific CD4 T cells identifies T-cell-intrinsic caspase-1 as an important regulator of Th17 differentiation

Gao

Deason

Jain

et al. 2018

Preprint

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One sentence summaryOur study revealed that DCs shape distinct pathogen-specific CD4 T cell transcriptome and from which, we discovered an unexpected role for T-cell-intrinsic caspase-1 in promoting Th17 differentiation.ABSTRACTDendritic cells (DCs) are critical for priming and differentiation of pathogen-specific CD4 T cells. However, to what extent innate cues from DCs dictate transcriptional changes in T cells leading to effector heterogeneity remains elusive. Here we have used an in vitro approach to prime naïve CD4 T cells by DCs stimulated with distinct pathogens. We have found that such pathogen-primed CD4 T cells express unique transcriptional profiles dictated by the nature of the priming pathogen. In contrast to cytokine-polarized Th17 cells that display signatures of terminal differentiation, pathogen-primed Th17 cells maintain a high degree of heterogeneity and plasticity. Further analysis identified caspase-1 as one of the genes upregulated only in pathogen-primed Th17 cells but not in cytokine-polarized Th17 cells. T-cell-intrinsic caspase-1, independent of its function in inflammasome, is critical for inducing optimal pathogen-driven Th17 responses. More importantly, T cells lacking caspase-1 fail to induce colitis following transfer into RAG-deficient mice, further demonstrating the importance of caspase-1 for the development of pathogenic Th17 cells in vivo. This study underlines the importance of DC-mediated priming in identifying novel regulators of T cell differentiation.

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“…Differentiation to Th17 cells in lymphoid organs is contingent on the presence of TGF-β1, IL-6 and IL-1β cytokines, while their effector function and pathogenicity relies on IL-23. In agreement with their high potential to induce Th17 cell differentiation, intestinal dendritic cells (DCs) are a major source of IL-23, IL-6 and IL-1β 5,6 . Of note, mice lacking a specific DC subtype characterized by the expression of CD11b and CD103 have reduced numbers of Th17 cells 6 , highlighting the important role of myeloid cells in Th17 cell homeostasis.…”

Section: Introductionmentioning

confidence: 96%

Liver X Receptor regulates Th17 and RORγt⁺ Treg cells by distinct mechanisms

Parigi

Das

Frede

et al. 2019

Preprint

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22The gastrointestinal microenvironment, dominated by dietary compounds and the commensal bacteria, 23 is a major driver of intestinal CD4 + T helper (Th) cell differentiation. Dietary compounds can be sensed 24 by nuclear receptors (NRs) that consequently exerts pleiotropic effects including immune modulation. 25However, how NRs regulate distinct intestinal Th subsets remain poorly understood. Here, we found 26 that under homeostatic condition Liver X receptor (LXR), a sensor of cholesterol metabolites, controls 27RORγt + Treg and Th17 cells in the intestine draining mesenteric lymph node (MLN). Mechanistically, 28 while lack of LXR signaling in CD11c + myeloid cells led to an increase in RORγt + Treg, modulation 29 of MLN Th17 was independent of LXR signaling in either immune or epithelial cells. Of note, LXRα 30 modulated only the Th17 cells, but not RORγt + Treg in the MLN and horizontal transfer of microbiota 31 between LXRα −/− and WT mice was sufficient to partially increase the MLN Th17 in WT mice. While 32LXRα deficiency increased the abundance of Ruminococcaceae and Lachnospiraceae bacterial 33 families compared to the WT littermates, microbiota ablation including ablation of SFB was not 34 sufficient to dampen LXRα-mediated expansion of MLN Th17. Altogether, our results suggest that 35 LXR modulates RORγt + Treg and Th17 cells in the MLN through distinct mechanisms.The intestinal barrier is continuously exposed to the changing external environment. To face this 56 challenge, our immune system has evolved to rapidly adapt to environmental changes by mounting 57 tolerogenic and effector responses on demand. A dynamic equilibrium between these two arms of the 58 immune system is required to maintain homeostasis, and failure of mounting an appropriate regulatory 59 response may lead to uncontrolled inflammatory reactions and chronic immune disorders. 60Owing to their ability to react in an antigen-specific manner CD4 + T helper (Th) cells are central 61 players in ensuring a protective response while limiting collateral damage. Mounting a functional Th 62 cell response in the intestine relies on the anatomical distribution of T cells in immunological inductive 63 and effector sites, where the former is constituted by intestine-draining lymphoid structures such as 64 MLN and the latter being the intraepithelial and lamina propria compartments 1 . The inductive sites 65 represent the arena where naïve CD4 + T cells encounter their cognate antigens for the first time and 66 functionally commit to specific effector subsets. Under steady state, retinoic acid-related orphan 67 receptor gt (RORgt) + Th cells (Th17) and Foxp3 expressing regulatory T cells (Treg) are the most 68 represented Th subsets in the MLN. Despite a certain degree of lineage and functional flexibility, Th17 69 and Treg cells play complementary roles in maintaining intestinal homeostasis. Although the 70 expression of RORgt and Foxp3 was originally thought to be mutually exclusive, a distinct new 71 population of RORgt + Foxp3 + regulatory T ...

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T H 17 cell plasticity: The role of dendritic cells and molecular mechanisms

Cited by 51 publications

References 99 publications

The Innate Immune Cell Profile of the Cornea Predicts the Onset of Ocular Surface Inflammatory Disorders

The Innate Immune Cell Profile of the Cornea Predicts the Onset of Ocular Surface Inflammatory Disorders

Transcriptome profiling of pathogen-specific CD4 T cells identifies T-cell-intrinsic caspase-1 as an important regulator of Th17 differentiation

Liver X Receptor regulates Th17 and RORγt⁺ Treg cells by distinct mechanisms

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T H 17 cell plasticity: The role of dendritic cells and molecular mechanisms

Cited by 51 publications

References 99 publications

The Innate Immune Cell Profile of the Cornea Predicts the Onset of Ocular Surface Inflammatory Disorders

The Innate Immune Cell Profile of the Cornea Predicts the Onset of Ocular Surface Inflammatory Disorders

Transcriptome profiling of pathogen-specific CD4 T cells identifies T-cell-intrinsic caspase-1 as an important regulator of Th17 differentiation

Liver X Receptor regulates Th17 and RORγt+ Treg cells by distinct mechanisms

Contact Info

Product

Resources

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T H 17 cell plasticity: The role of dendritic cells and molecular mechanisms

Liver X Receptor regulates Th17 and RORγt⁺ Treg cells by distinct mechanisms