The retinoic acid receptor drives neuroinflammation and fine tunes the homeostasis of interleukin-17-producing T cells
Agerholm, R.; Rizk, J.; Kadekar, D.; Borch, A.; Hadrup, S. R.; Bekiaris, V.
Show abstract
The vitamin A metabolite retinoic acid (RA) is critical for the maturation and function of the immune system, however, our knowledge regarding its role in gamma delta ({gamma}{delta}) T cells is limited. By specifically inactivating the RA receptor alpha (RAR) in type 3 lymphocytes and using a combination of fetal thymic organ cultures and single-cell RNA-sequencing we found that RA strengthened TCR signaling to limit the embryonic development of interleukin(IL)-17-producing {gamma}{delta} T cells ({gamma}{delta}T17), while at the same time it promoted their survival after birth. In adult mice, RA imposed a multi-level transcriptional program allowing {gamma}{delta}T17 cells to become activated, survive and sense interferon. Consequently, cells with inactive RAR responded poorly to immunization and produced low level of cytokines leading to near disease resistance in the experimental autoimmune encephalomyelitis model. Finally, RA was required for optimal expression of the 4{beta}1 integrin and {gamma}{delta}T17 cell infiltration to the brain. Collectively, these studies suggest that by acting at various stages during the lifetime of {gamma}{delta} T cells, RA supports their normal development, their survival and their ability to respond to inflammatory stimuli.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Targeting interferon-{lambda} signaling promotes recovery from central nervous system autoimmunity 97%
- A defect in thymic tolerance causes T cell-mediated autoimmunity in a murine model of COPA syndrome 97%
- Context-dependent miR-21 regulation of TLR7-mediated autoimmune and foreign antigen driven antibody-forming cell and germinal center responses 96%
Similar papers in this journal
- TGF-β broadly modifies rather than specifically suppresses reactivated memory CD8 T cells in a dose-dependent manner 96%
- T Lymphocyte-Specific Deletion of SHP1 and SHP2 Promotes Activation-Induced Cell Death of CD4+ T Cells and Impairs Antitumor Response 96%
- Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism 95%
Similar papers in this journal
- Neurotrophic factor Neuritin modulates T cell electrical and metabolic state for the balance of tolerance and immunity 96%
- Integration of IL-2 and IL-4 Signals Coordinates Divergent Regulatory T cell Responses and Drives Therapeutic Efficacy 96%
- Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis 96%
Similar papers in this journal
- Type I interferons promote germinal centers through B cell intrinsic signaling and dendritic cell dependent Th1 and Tfh cell lineages 96%
- H2-O deficiency promotes regulatory T cell differentiation and CD4 T cell hyperactivity 96%
- Hemoglobin alpha regulates T-lymphocyte activation and mitochondrial function 96%
Similar papers in this journal
- OCA-B promotes pathogenic maturation 1 of stem-like CD4+ T cells and autoimmune demyelination 97%
- A20's Linear Ubiquitin Binding Motif Restrains Pathogenic Activation of TH17/22 cells and IL-22 Driven Enteritis 96%
- Natural killer cell immunosuppressive function requires CXCR3-dependent redistribution within lymphoid tissues 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.