Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage Journal Article
| Authors: | Lemarquis, A. L.; Kousa, A. I.; Argyropoulos, K. V.; Jahn, L.; Gipson, B.; Pierce, J.; Serrano-Marin, L.; Victor, K.; Kanno, Y.; Girotra, N. N.; Andrlova, H.; Tsai, J.; Velardi, E.; Sharma, R.; Grassmann, S.; Ekwall, O.; Goldstone, A. B.; Dudakov, J. A.; DeWolf, S.; van den Brink, M. R. M. |
| Article Title: | Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage |
| Abstract: | Thymic injury associated with disease or cancer treatment reduces T cell production and makes patients more vulnerable to infections and cancers. Here, we examined the role of regulatory T (Treg) cells on thymic regeneration. Treg cell frequencies increased in the thymus in various acute injury models. Depletion of Treg cells impaired thymic regeneration, impacting both the thymocyte compartment and the stromal cell compartment; adoptive transfer of Treg cells enhanced regeneration. Expansion of circulating Treg cells, as opposed to that of tissue resident or recent thymic emigrants, explained this increase, as seen using parabiotic and adoptive transfer models. Single-cell analyses of recirculating Treg cells revealed expression of various regenerative factors, including the cytokine amphiregulin. Deletion of amphiregulin in these Treg cells impaired regeneration in the injured thymus. We identified an analogous population of CD39+ICOS+ Treg cells in the human thymus. Our findings point to potential therapeutic avenues to address aging- and treatment-induced immunosuppression. © 2025 The Authors |
| Keywords: | epidermal growth factor; mitogen activated protein kinase; child; controlled study; unclassified drug; promoter region; gene deletion; nonhuman; cd8 antigen; transcription factor foxp3; animal cell; mouse; animal tissue; stat3 protein; transforming growth factor beta; epidermal growth factor receptor; animal experiment; animal model; tissue regeneration; cyclophosphamide; dexamethasone; immunoglobulin enhancer binding protein; protein serine threonine kinase; regulatory t lymphocyte; thymus; population; mitogen activated protein kinase 1; adoptive transfer; lipopolysaccharide; aging; cd4 antigen; rag2 protein; cytotoxic t lymphocyte antigen 4; immunosuppressive treatment; stroma cell; stat5 protein; glucocorticoid induced tumor necrosis factor receptor; thymocyte; cell expansion; cd134 antigen; thymus function; thymus cancer; tissue repair; injury; diphtheria toxin; amphiregulin; interleukin 2 receptor alpha; tumor necrosis factor; broxuridine; interleukin 18; immune reconstitution; thymic regeneration; chemokine receptor cxcr4; single cell analysis; interleukin 7 receptor; chemokine receptor ccr6; cd81 antigen; protein fos; thymus disease; treg cells; retinoid related orphan receptor alpha; human; male; article; ikzf2 protein; tregs; areg protein; receptor type tyrosine protein phosphatase c; tumor necrosis factor receptor superfamily member 9; cd39 antigen; trefoil factor 1; gzmk protein; parabiosis; recirculating tregs; cish protein; ikz2 protein; ikz4 protein; ikzf4 protein; klrg1 protein; mapk3 protein; penk protein; sdc4 protein; zfp36l1 protein |
| Journal Title: | Immunity |
| Volume: | 58 |
| Issue: | 2 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2025-02-11 |
| Start Page: | 397 |
| End Page: | 411.e6 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2025.01.006 |
| PROVIDER: | scopus |
| PUBMED: | 39892391 |
| PMCID: | PMC11932356 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus |
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