First Author | Prizant H | Year | 2021 |
Journal | Cell Rep | Volume | 36 |
Issue | 6 | Pages | 109523 |
PubMed ID | 34380032 | Mgi Jnum | J:314353 |
Mgi Id | MGI:6765701 | Doi | 10.1016/j.celrep.2021.109523 |
Citation | Prizant H, et al. (2021) CXCL10(+) peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter. Cell Rep 36(6):109523 |
abstractText | Correct positioning of T cells within infected tissues is critical for T cell activation and pathogen control. Upon tissue entry, effector T cells must efficiently locate antigen-presenting cells (APC) for peripheral activation. We reveal that tissue entry and initial peripheral activation of Th1 effector T cells are tightly linked to perivascular positioning of chemokine-expressing APCs. Dermal inflammation induces tissue-wide de novo generation of discrete perivascular CXCL10(+) cell clusters, enriched for CD11c(+)MHC-II(+) monocyte-derived dendritic cells. These chemokine clusters are "hotspots" for both Th1 extravasation and activation in the inflamed skin. CXCR3-dependent Th1 localization to the cluster micro-environment prolongs T-APC interactions and boosts function. Both the frequency and range of these clusters are enhanced via a T helper 1 (Th1)-intrinsic, interferon-gamma (IFNgamma)-dependent positive-feedback loop. Thus, the perivascular CXCL10(+) clusters act as initial peripheral activation niches, optimizing controlled activation broadly throughout the tissue by coupling Th1 tissue entry with enhanced opportunities for Th1-APC encounter. |