A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Lymphatic Endothelial Cell Activation and Dendritic Cell Transmigration Is Modified by Genetic Deletion of Clever-1
Tekijät: Tadayon Sina, Dunkel Johannes, Takeda Akira, Eichin Dominik, Virtakoivu Reetta, Elima Kati, Jalkanen Sirpa, Hollmen Maija
Kustantaja: FRONTIERS MEDIA SA
Julkaisuvuosi: 2021
Journal: Frontiers in Immunology
Tietokannassa oleva lehden nimi: FRONTIERS IN IMMUNOLOGY
Lehden akronyymi: FRONT IMMUNOL
Artikkelin numero: ARTN 602122
Vuosikerta: 12
Sivujen määrä: 15
ISSN: 1664-3224
eISSN: 1664-3224
DOI: https://doi.org/10.3389/fimmu.2021.602122
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/Publication/54579713
Clever-1 also known as Stabilin-1 and FEEL-1 is a scavenger molecule expressed on a subpopulation of anti-inflammatory macrophages and lymphatic endothelial cells (LECs). However, its role in regulating dendritic cell (DC) trafficking and subsequent effects on immunity have remained unexplored. In this study, we demonstrate that DC trafficking from the skin into the draining lymph nodes is compromised in the absence of Clever-1. By adoptive transfer approaches we further show that the poor trafficking is due to the impaired entrance of DCs into afferent lymphatics. Despite this, injections of ovalbumin-loaded DCs into the footpads induced a stronger proliferative response of OT II T cells in the draining lymph nodes. This could be explained by the increased MHC II expression on DCs and a less tolerogenic phenotype of LECs in lymph nodes of Clever-1 knockout mice. Thus, although fewer DCs reach the nodes, they are more active in creating antigen-specific immune responses. This suggests that the DCs migrating to the draining lymph node within Clever-1 positive lymphatics experience immunosuppressive interactions with LECs. In conclusion, besides being a trafficking molecule on lymphatic vasculature Clever-1 is immunosuppressive towards migrating DCs and thus, regulates the magnitude of immune responses created by incoming DCs in the draining lymph nodes.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
