Novel self-amplificatory loop between T cells and tenocytes as a driver of chronicity in tendon disease
| Autor: | Lucy MacDonald, Umberto G. Fazzi, Neal L. Millar, Emma Garcia-Melchor, Iain B. McInnes, Lindsay A. N. Crowe, Shatakshi Sood, Giacomo Cafaro, Michael McLean, Moeed Akbar |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Stromal cell medicine.medical_treatment T cell T-Lymphocytes Immunology General Biochemistry Genetics and Molecular Biology Collagen Type I Proinflammatory cytokine Tendons 03 medical and health sciences 0302 clinical medicine Rheumatology Immunology and Allergy Medicine T-lymphocyte subsets Humans tendinopathy Cells Cultured 030203 arthritis & rheumatology Cluster of differentiation business.industry Cell adhesion molecule Cell biology Miscellaneous Tenocytes Collagen type I alpha 1 030104 developmental biology Cytokine medicine.anatomical_structure inflammation Culture Media Conditioned T cell migration Cytokines Collagen business |
| Zdroj: | Annals of the Rheumatic Diseases |
| ISSN: | 1468-2060 0003-4967 |
| Popis: | ObjectivesIncreasing evidence suggests that inflammatory mechanisms play a key role in chronic tendon disease. After observing T cell signatures in human tendinopathy, we explored the interaction between T cells and tendon stromal cells or tenocytes to define their functional contribution to tissue remodelling and inflammation amplification and hence disease perpetuation.MethodsT cells were quantified and characterised in healthy and tendinopathic tissues by flow cytometry (FACS), imaging mass cytometry (IMC) and single cell RNA-seq. Tenocyte activation induced by conditioned media from primary damaged tendon or interleukin-1β was evaluated by qPCR. The role of tenocytes in regulating T cell migration was interrogated in a standard transwell membrane system. T cell activation (cell surface markers by FACS and cytokine release by ELISA) and changes in gene expression in tenocytes (qPCR) were assessed in cocultures of T cells and explanted tenocytes.ResultsSignificant quantitative differences were observed in healthy compared with tendinopathic tissues. IMC showed T cells in close proximity to tenocytes, suggesting tenocyte–T cell interactions. On activation, tenocytes upregulated inflammatory cytokines, chemokines and adhesion molecules implicated in T cell recruitment and activation. Conditioned media from activated tenocytes induced T cell migration and coculture of tenocytes with T cells resulted in reciprocal activation of T cells. In turn, these activated T cells upregulated production of inflammatory mediators in tenocytes, while increasing the pathogenic collagen 3/collagen 1 ratio.ConclusionsInteraction between T cells and tenocytes induces the expression of inflammatory cytokines/chemokines in tenocytes, alters collagen composition favouring collagen 3 and self-amplifies T cell activation via an auto-regulatory feedback loop. Selectively targeting this adaptive/stromal interface may provide novel translational strategies in the management of human tendon disorders. |
| Databáze: | OpenAIRE |
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