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Lymphotoxin α fine-tunes T cell clonal deletion by regulating thymic entry of antigen-presenting cells

Abstract : Medullary thymic epithelial cells (mTEC) purge the T cell repertoire of autoreactive thy-mocytes. Although dendritic cells (DC) reinforce this process by transporting innocuous peripheral self-antigens, the mechanisms that control their thymic entry remain unclear. Here we show that mTEC-CD4 + thymocyte crosstalk regulates the thymus homing of SHPS-1 + conventional DCs (cDC), plasmacytoid DCs (pDC) and macrophages. This homing process is controlled by lymphotoxin α (LTα), which negatively regulates CCL2, CCL8 and CCL12 chemokines in mTECs. Consequently, Ltα-deficient mice have increased expression of these chemokines that correlates with augmented classical NF-κB subunits and increased thymic recruitment of cDCs, pDCs and macrophages. This enhanced migration depends mainly on the chemokine receptor CCR2, and increases thymic clonal deletion. Altogether, this study identifies a fine-tuning mechanism of T cell repertoire selection and paves the way for therapeutic interventions to treat autoimmune disorders.
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https://www.hal.inserm.fr/inserm-02438492
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Submitted on : Tuesday, January 14, 2020 - 11:37:06 AM
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Noella Lopes, Jonathan Charaix, Oriane Cédile, Arnauld Sergé, Magali Irla. Lymphotoxin α fine-tunes T cell clonal deletion by regulating thymic entry of antigen-presenting cells. Nature Communications, Nature Publishing Group, 2018, 9 (1), pp.1262. ⟨10.1038/s41467-018-03619-9⟩. ⟨inserm-02438492⟩

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