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. 2025 Feb 11;58(2):397-411.e6.
doi: 10.1016/j.immuni.2025.01.006. Epub 2025 Jan 31.

Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage

Andri L Lemarquis  1 , Anastasia I Kousa  2 , Kimon V Argyropoulos  3 , Lorenz Jahn  4 , Brianna Gipson  4 , Jonah Pierce  5 , Lucia Serrano-Marin  4 , Kristen Victor  4 , Yuzuka Kanno  4 , Narina N Girotra  4 , Hana Andrlova  4 , Jennifer Tsai  4 , Enrico Velardi  6 , Roshan Sharma  7 , Simon Grassmann  4 , Olov Ekwall  8 , Andrew B Goldstone  9 , Jarrod A Dudakov  10 , Susan DeWolf  11 , Marcel R M van den Brink  12
Affiliations

Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage

Andri L Lemarquis et al. Immunity. .

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.

Keywords: Treg cells; Tregs; aging; amphiregulin; immune reconstitution; injury; parabiosis; recirculating Tregs; thymic regeneration; thymus.

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Conflict of interest statement

Declaration of interests Dr. M.R.M.v.d.B has received research support and stock options from Seres Therapeutics and stock options from Notch Therapeutics and Pluto Therapeutics; has received royalties from Wolters Kluwer; has consulted, received honoraria from, or participated in advisory boards for Seres Therapeutics, Rheos Medicines, Ceramedix, Pluto Therapeutics, Thymofox, Garuda, Novartis (spouse), Synthekine (spouse), Beigene (spouse), and Kite (spouse); has IP licensing with Seres Therapeutics and Juno Therapeutics; and holds a fiduciary role on the Foundation Board of DKMS (a nonprofit organization).

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