Zusammenfassung
Interleukin 17-producing gamma delta T (gamma delta T17) cells have unconventional trafficking characteristics, residing in mucocutaneous tissues but also homing into inflamed tissues via circulation. Despite being fundamental to gamma delta T17-driven early protective immunity and exacerbation of autoimmunity and cancer, migratory cues controlling gamma delta T17 cell positioning in barrier ...
Zusammenfassung
Interleukin 17-producing gamma delta T (gamma delta T17) cells have unconventional trafficking characteristics, residing in mucocutaneous tissues but also homing into inflamed tissues via circulation. Despite being fundamental to gamma delta T17-driven early protective immunity and exacerbation of autoimmunity and cancer, migratory cues controlling gamma delta T17 cell positioning in barrier tissues and recruitment to inflammatory sites are still unclear. Here we show that gamma delta T17 cells constitutively express chemokine receptors CCR6 and CCR2. While CCR6 recruits resting gamma delta T17 cells to the dermis, CCR2 drives rapid gamma delta T17 cell recruitment to inflamed tissues during autoimmunity, cancer and infection. Downregulation of CCR6 by IRF4 and BATF upon gamma delta T17 activation is required for optimal recruitment of gamma delta T17 cells to inflamed tissue by preventing their sequestration into uninflamed dermis. These findings establish a lymphocyte trafficking model whereby a hierarchy of homing signals is prioritized by dynamic receptor expression to drive both tissue surveillance and rapid recruitment of gamma delta T17 cells to inflammatory lesions.
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