The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Extrathymic Generation of Regulatory T Cells in Placental Mammals Mitigates Maternal-Fetal Conflict
Open accessAbstract
Summary Regulatory T (Treg) cells, whose differentiation and function are controlled by X-chromosome-encoded transcription factor Foxp3, are generated in the thymus (tTreg) and extrathymically (peripheral, pTreg) and their deficiency results in fatal autoimmunity. Here we demonstrate that a Foxp3 enhancer, conserved non-coding sequence 1 (CNS1), essential for pTreg, but dispensable for tTreg cell generation, is present only in placental mammals. CNS1 is largely composed of mammalian-wide interspersed repeats (MIR) that have undergone retrotransposition during early mammalian radiation. During pregnancy pTreg cells specific to a model paternal alloantigen were generated in a CNS1-dependent manner and accumulated in the placenta. Furthermore, when mated with allogeneic, but not syngeneic males, CNS1-deficient females showed increased fetal resorption accompanied by increased immune cell infiltration and defective remodeling of spiral arteries. Our results suggest that during evolution a CNS1-dependent mechanism of extrathymic differentiation of Treg cells emerged in placental animals to enforce maternal-fetal tolerance.
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Cites
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Metadata
- Authors
- Samstein, R. M., Josefowicz, S. Z., Arvey, A., Treuting, P. M., & Rudensky, A. Y.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 150
- Issue
- 1
- Pages
- 29-38
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2072509185
- Cited by
- 623
- References
- 51
- FWCI
- 25.27
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Samstein, R. M., Josefowicz, S. Z., Arvey, A., Treuting, P. M., & Rudensky, A. Y. (2012). Extrathymic Generation of Regulatory T Cells in Placental Mammals Mitigates Maternal-Fetal Conflict. Cell. https://doi.org/10.1016/j.cell.2012.05.031
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