ArticleProceedings of the National Academy of Sciences of the United States of America2010
TGF-beta regulates T-cell neurokinin-1 receptor internalization and function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Mechano responsiveness of neuroimmune cross-talk in bone and joints: A narrative review with implications for force-based manipulations.Musculoskeletal science & practice · 2026Review
- Mucosal neuroimmune mechanisms in gastro-oesophageal reflux disease (GORD) pathogenesis.Journal of gastroenterology · 2024Review
- Cellular and Molecular Roles of Immune Cells in the Gut-Brain Axis in Migraine.Molecular neurobiology · 2024Review
- From pain to tumor immunity: influence of peripheral sensory neurons in cancer.Frontiers in immunology · 2024Review
- Neurokinin-2 receptor negatively modulates substance P responses by forming complex with Neurokinin-1 receptor.Cell & bioscience · 2023Article
- Neuroimmune regulation in Hirschsprung's disease associated enterocolitis.Frontiers in immunology · 2023Review
- Immunomodulatory Role of Neuropeptides in the Cornea.Biomedicines · 2022Review
- Review
- Neurokinin receptors and their implications in various autoimmune diseases.Current research in immunology · 2021Review
- Biomarkers and Their Possible Functions in the Intestinal Microenvironment of Chagasic Megacolon: An Overview of the (Neuro)inflammatory Process.Journal of immunology research · 2021Review
- The Role of Nociceptive Neurons in the Pathogenesis of Psoriasis.Frontiers in immunology · 2020Review
- Functional heterogeneity of human tissue-resident memory T cells based on dye efflux capacities.JCI insight · 2018Article
- Article
- Substance P increases CCN2 dependent on TGF-beta yet Collagen Type I via TGF-beta1 dependent and independent pathways in tenocytes.Connective tissue research · 2018Article
- Enhanced expressions of neurodegeneration-associated factors, UPS impairment, and excess Aβ accumulation in the hippocampus of mice with persistent cerebral toxocariasis.Parasites & vectors · 2017Article
- Neuropeptide substance P and the immune response.Cellular and molecular life sciences : CMLS · 2016Review
- Transforming Growth Factor Beta 1 Modulates the Functional Expression of the Neurokinin-1 Receptor in Human Keratocytes.Current eye research · 2016Article
- Predominance of synovial sensory nerve fibers in arthrofibrosis following total knee arthroplasty compared to osteoarthritis of the knee.Journal of orthopaedic surgery and research · 2016Article
- The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders.Frontiers in cellular neuroscience · 2016Review
- Reciprocal Regulation of Substance P and IL-12/IL-23 and the Associated Cytokines, IFNγ/IL-17: A Perspective on the Relevance of This Interaction to Multiple Sclerosis.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Substance P (SP) is a proinflammatory mediator implicated in inflammatory bowel disease (IBD) and other inflammatory states. SP acts by stimulating the neurokinin-1 receptor (NK-1R) on T lymphocytes and other cell types, and regulates these cells in a complex interplay with multiple cytokines. The mechanisms of interaction among these inflammatory mediators are not yet fully understood. Here, we demonstrate that function of the NK-1R, a member of the G protein-coupled receptor (GPCR) superfamily, is modulated by TGF-beta. The latter acts not on a GPCR but via serine-threonine kinase-class receptors. By flow confocal image analysis, we demonstrate that TGF-beta delays SP-induced NK-1R internalization on mucosal T cells isolated from a mouse model of IBD and on granuloma T cells in murine schistosomiasis. Furthermore, luciferase reporter-gene assays revealed that NK-1R stimulation activates the nuclear factor of activated T cell- and activator protein-1-dependent signaling pathways, which are known triggers of effector T-cell cytokine production. TGF-beta markedly increases SP-induced activation of these signaling cascades, suggesting that delayed NK-1R internalization results in enhanced signaling. Providing a link to amplified immune function, SP and TGF-beta, when applied in combination, trigger a strong release of the proinflammatory cytokines IFN-gamma and IL17 from intestinal inflammatory T cells, whereas either agonist alone shows no effect. These observations establish precedent that members of two distinct receptor superfamilies can interact via a previously unrecognized mechanism, and reveal a paradigm of GPCR transregulation that is relevant to IBD and possibly other disease processes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.