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

Author

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  • Noëlla Lopes

    (INSERM U1104, CNRS UMR7280, Aix-Marseille Université UM2)

  • Jonathan Charaix

    (INSERM U1104, CNRS UMR7280, Aix-Marseille Université UM2)

  • Oriane Cédile

    (University of Southern Denmark)

  • Arnauld Sergé

    (Institut Paoli-Calmettes, INSERM U1068, CNRS UMR7258, Aix-Marseille Université UM105)

  • Magali Irla

    (INSERM U1104, CNRS UMR7280, Aix-Marseille Université UM2)

Abstract

Medullary thymic epithelial cells (mTEC) purge the T cell repertoire of autoreactive thymocytes. 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.

Suggested Citation

  • Noëlla Lopes & Jonathan Charaix & Oriane Cédile & Arnauld Sergé & Magali Irla, 2018. "Lymphotoxin α fine-tunes T cell clonal deletion by regulating thymic entry of antigen-presenting cells," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03619-9
    DOI: 10.1038/s41467-018-03619-9
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