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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\u2212 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.<\/jats:p>","DOI":"10.4049\/jimmunol.2101046","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T05:01:58Z","timestamp":1672722118000},"page":"1942-1949","source":"Crossref","is-referenced-by-count":17,"title":["IL-7 Receptor Drives Early T Lineage Progenitor Expansion"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0657-2283","authenticated-orcid":false,"given":"Rafael A","family":"Paiva","sequence":"first","affiliation":[{"name":"Lymphocyte Development and Leukemogenesis Laboratory, Instituto Gulbenkian de Ci\u00eancia, Calouste Gulbenkian Foundation , Oeiras,","place":["Portugal"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila V","family":"Ramos","sequence":"additional","affiliation":[{"name":"Lymphocyte Development and Leukemogenesis Laboratory, Instituto Gulbenkian de Ci\u00eancia, Calouste Gulbenkian Foundation , Oeiras,","place":["Portugal"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4548-5211","authenticated-orcid":false,"given":"Gon\u00e7alo","family":"Leiria","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit, Instituto Gulbenkian de Ci\u00eancia, Calouste Gulbenkian Foundation , Oeiras,","place":["Portugal"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8717-9709","authenticated-orcid":false,"given":"Vera C","family":"Martins","sequence":"additional","affiliation":[{"name":"Lymphocyte Development and Leukemogenesis Laboratory, Instituto Gulbenkian de Ci\u00eancia, Calouste Gulbenkian Foundation , Oeiras,","place":["Portugal"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"2025021008411614000_r1","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/nri3702","article-title":"Developmental gene networks: a triathlon on the course to T cell identity","volume":"14","author":"Yui","year":"2014","journal-title":"Nat. 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