What question did this study set out to answer?

To determine how endosomal trafficking and receptor turnover regulate TLR7 signaling to prevent autoimmune disease in humans.

January 11, 2024Science ImmunologyOpen Access

Disrupted degradative sorting of TLR7 is associated with human lupus

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To determine how endosomal trafficking and receptor turnover regulate TLR7 signaling to prevent autoimmune disease in humans.
Investigated the molecular interactions among the TLR7-associated trafficking factor Unc93b1, the BORC complex, and the small GTPase Arl8b.
Evaluated endosomal TLR7 degradation and signaling dynamics in a patient presenting with childhood-onset systemic lupus erythematosus.
The late endosomal BORC complex and Arl8b directly interact with Unc93b1 to control intracellular TLR7 abundance through receptor turnover.
A patient mutation in UNC93B1 disrupted BORC binding, leading to endosomal TLR7 accumulation, broken nucleic acid tolerance, and childhood-onset lupus.

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Implication

Molecular study demonstrates that disrupted TLR7 receptor degradation drives autoimmune signaling in childhood-onset lupus, highlighting the endomembrane system's role in immune tolerance.

Cite This Study

Mishra et al. (2024) studied this question.

synapsesocial.com/papers/6a83d1053fd01c19a6c580e7 https://doi.org/10.1126/sciimmunol.adi9575

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Implication

Molecular study demonstrates that disrupted TLR7 receptor degradation drives autoimmune signaling in childhood-onset lupus, highlighting the endomembrane system's role in immune tolerance.

Disrupted degradative sorting of TLR7 is associated with human lupus

Key Points

Discussion

Implication

Cite This Study

Disrupted degradative sorting of TLR7 is associated with human lupus

Key Points

Discussion

Implication

Cite This Study

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