In:
Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-3-22)
Abstract:
Precisely controlled lymphocyte migration is critically required for immune surveillance and successful immune responses. Lymphocyte migration is strictly regulated by chemokines and chemokine receptors. Here we show that protein geranylgeranylation, a form of post-translational protein lipid modification, is required for chemokine receptor-proximal signaling. Mature thymocytes deficient for protein geranylgeranylation are impaired for thymus egress. Circulating mature T cells lacking protein geranylgeranylation fail to home to secondary lymphoid organs or to transmigrate in response to chemokines in vitro . Mechanistically, protein geranylgeranylation modifies the γ-subunits of the heterotrimeric small GTPases that are essential for chemokine receptor signaling. In addition, protein geranylgeranylation also promotes the differentiation of IL-17-producing T helper cells while inhibiting the differentiation of Foxp3 + regulatory T cells. Finally, mice with T cell lineage-specific deficiency of protein geranylgeranylation are resistant to experimental autoimmune encephalomyelitis induction. This study elucidated a critical role of protein geranylgeranylation in regulating T lymphocyte migration and function.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2021.641188
DOI:
10.3389/fimmu.2021.641188.s001
DOI:
10.3389/fimmu.2021.641188.s002
DOI:
10.3389/fimmu.2021.641188.s003
DOI:
10.3389/fimmu.2021.641188.s004
DOI:
10.3389/fimmu.2021.641188.s005
DOI:
10.3389/fimmu.2021.641188.s006
DOI:
10.3389/fimmu.2021.641188.s007
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2606827-8
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