Controlled WASp activity regulates the proliferative response for Treg cell differentiation in the thymus.

Autor: Vasconcelos-Fontes L; Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.; Laboratory on Thymus Research, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.; National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil., Vieira RC; Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., He M; Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Ferreira-Reis R; Laboratory on Thymus Research, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.; National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.; Rio de Janeiro Research Network on Neuroinflammation (RENEURIN), Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil., Jurberg AD; Laboratory on Thymus Research, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.; National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.; Rio de Janeiro Research Network on Neuroinflammation (RENEURIN), Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil., Arêas Mendes-da-Cruz D; Laboratory on Thymus Research, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.; National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.; Rio de Janeiro Research Network on Neuroinflammation (RENEURIN), Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil., Andersson J; Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.; Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden., Cotta-de-Almeida V; Laboratory on Thymus Research, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.; National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.; Rio de Janeiro Research Network on Neuroinflammation (RENEURIN), Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil., Westerberg LS; Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2024 May; Vol. 54 (5), pp. e2350450. Date of Electronic Publication: 2024 Feb 14.
DOI: 10.1002/eji.202350450
Abstrakt: The Wiskott-Aldrich syndrome protein (WASp) regulates actin cytoskeletal dynamics and function of hematopoietic cells. Mutations in the WAS gene lead to two different syndromes; Wiskott-Aldrich syndrome (WAS) caused by loss-of-function mutations, and X-linked neutropenia (XLN) caused by gain-of-function mutations. We previously showed that WASp-deficient mice have a decreased number of regulatory T (Treg) cells in the thymus and the periphery. We here evaluated the impact of WASp mutations on Treg cells in the thymus of WAS and XLN mouse models. Using in vitro Treg differentiation assays, WAS CD4 single-positive thymocytes have decreased differentiation to Treg cells, despite normal early signaling upon IL-2 and TGF-β stimulation. They failed to proliferate and express CD25 at high levels, leading to poor survival and a lower number of Foxp3 + Treg cells. Conversely, XLN CD4 single-positive thymocytes efficiently differentiate into Foxp3 + Treg cells following a high proliferative response to IL-2 and TGF-β, associated with high CD25 expression when compared with WT cells. Altogether, these results show that specific mutations of WASp affect Treg cell development differently, demonstrating a critical role of WASp activity in supporting Treg cell development and expansion.
(© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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