Journal
JOURNAL OF IMMUNOLOGY
Volume 209, Issue 10, Pages 1942-1949Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2101046
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Funding
- Instituto Gulbenkian de Ciencia
- Calouste Gulbenkian Foundation
- Portuguese National Research Council (Fundacao para a Cienciae Tecnologia Grants) [PTDC/BIA-BID/30925/2017, PTDC/MED-IMU/3649/2021]
- Fundacao para a Ciencia e Tecnologia Contract [CEECIND/03106/2018]
- Fundacao para a Ciencia e Tecnologia Ph.D. Fellowships [D/BD/114341/2016, PD/BD/139190/2018]
- Fundacao para a Ciencia e Tecnologia [LISBOA-01-0145-FEDER-022170, PPBI-POCI-01-0145-FEDER-022122]
- Lisboa2020, under PORTUGAL2020 agreement (European Regional Development Fund)
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IL-7/IL-7R is necessary for T lymphocyte differentiation by promoting proliferation and survival of the most immature thymocytes, leading to a significant decrease in the number of early T lineage progenitor cells.
IL-7 and IL-7R are essential for T lymphocyte differentiation by driving proliferation and survival of specific developmental stages. Although early T lineage progenitors (ETPs), the most immature thymocyte population known, have a history of IL-7R expression, it is unclear whether IL-7R is required at this stage. In this study, we show that mice lacking IL-7 or IL-7R have a marked loss of ETPs that results mostly from a cell-autonomous defect in proliferation and survival, although no changes were detected in Bcl2 protein levels. Furthermore, a fraction of ETPs responded to IL-7 stimulation ex vivo by phosphorylating Stat5, and IL-7R was enriched in the most immature Flt3(+)Ccr9(+) ETPs. Consistently, IL-7 promoted the expansion of Flt3(+) but not Flt3(-) ETPs on OP9-DLL4 cocultures, without affecting differentiation at either stage. Taken together, our data show that IL-7/IL-7R is necessary following thymus seeding by promoting proliferation and survival of the most immature thymocytes.
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