CXCL10(+) peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter
- Author(s)
- Prizant, H; Patil, N; Negatu, S; Bala, N; McGurk, A; Leddon, SA; Hughson, A; McRae, TD; Gao, YR; Livingstone, AM; Groom, JR; Luster, AD; Fowell, DJ;
- Details
- Publication Year 2021-08-10,Volume 36,Issue #6,Page 109523
- Journal Title
- Cell Reports
- Abstract
- 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 (IFNγ)-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.
- Publisher
- Cell Press
- Keywords
- CD4 T cells; Cxcl10; Cxcr3; Th1; chemokine; inflammation; intra-vital multiphoton microscopy; moDCs; perivascular; skin
- Research Division(s)
- Immunology
- PubMed ID
- 34380032
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2021.109523
- Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2021.109523- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-09-17 09:12:03
Last Modified: 2021-09-17 09:24:56