: Beside suppressing immune responses, regulatory T cells (Tregs) maintain tissue homeostasis and control systemic metabolism. Whether iron is involved in Treg-mediated tolerance is completely unknown. Here, we showed that the transferrin receptor CD71 was upregulated on activated Tregs infiltrating human liver cancer. Mice with a Treg-restricted CD71 deficiency spontaneously developed a scurfy-like disease, caused by impaired perinatal Treg expansion. CD71-null Tregs displayed decreased proliferation and tissue-Treg signature loss. In perinatal life, CD71 deficiency in Tregs triggered hepatic iron overload response, characterized by increased hepcidin transcription and iron accumulation in macrophages. Lower bacterial diversity, and reduction of beneficial species, were detected in the fecal microbiota of CD71 conditional knock-out neonates. Our findings indicate that CD71-mediated iron absorption is required for Treg perinatal expansion and related to systemic iron homeostasis and bacterial gut colonization. Therefore, we hypothesize that Tregs establish nutritional tolerance through competition for iron during bacterial colonization after birth.

Pacella, I., Pinzon Grimaldos, A., Rossi, A., Tucci, G., Zagaglioni, M., Potenza, E., et al. (2024). Iron capture through CD71 drives perinatal and tumor-associated Treg expansion. JCI INSIGHT [10.1172/jci.insight.167967].

Iron capture through CD71 drives perinatal and tumor-associated Treg expansion

Cancila, Valeria;Belmonte, Beatrice;Tripodo, Claudio;
2024-07-02

Abstract

: Beside suppressing immune responses, regulatory T cells (Tregs) maintain tissue homeostasis and control systemic metabolism. Whether iron is involved in Treg-mediated tolerance is completely unknown. Here, we showed that the transferrin receptor CD71 was upregulated on activated Tregs infiltrating human liver cancer. Mice with a Treg-restricted CD71 deficiency spontaneously developed a scurfy-like disease, caused by impaired perinatal Treg expansion. CD71-null Tregs displayed decreased proliferation and tissue-Treg signature loss. In perinatal life, CD71 deficiency in Tregs triggered hepatic iron overload response, characterized by increased hepcidin transcription and iron accumulation in macrophages. Lower bacterial diversity, and reduction of beneficial species, were detected in the fecal microbiota of CD71 conditional knock-out neonates. Our findings indicate that CD71-mediated iron absorption is required for Treg perinatal expansion and related to systemic iron homeostasis and bacterial gut colonization. Therefore, we hypothesize that Tregs establish nutritional tolerance through competition for iron during bacterial colonization after birth.
2-lug-2024
Settore MED/08 - Anatomia Patologica
Settore MED/05 - Patologia Clinica
Pacella, I., Pinzon Grimaldos, A., Rossi, A., Tucci, G., Zagaglioni, M., Potenza, E., et al. (2024). Iron capture through CD71 drives perinatal and tumor-associated Treg expansion. JCI INSIGHT [10.1172/jci.insight.167967].
File in questo prodotto:
File Dimensione Formato  
167967.1-20240701145934-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf

accesso aperto

Tipologia: Versione Editoriale
Dimensione 1.76 MB
Formato Adobe PDF
1.76 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/644853
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact