A1 Refereed original research article in a scientific journal
Clever-1 contributes to lymphocyte entry into the spleen via the red pulp
Authors: Tadayon S, Dunkel J, Takeda A, Halle O, Karikoski M, Gerke H, Rantakari P, Virtakoivu R, Pabst O, Salmi M, Hollmen M, Jalkanen S
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Publication year: 2019
Journal: Science Immunology
Journal name in source: SCIENCE IMMUNOLOGY
Journal acronym: SCI IMMUNOL
Article number: ARTN eaat0297
Volume: 4
Issue: 33
Number of pages: 11
ISSN: 2470-9468
eISSN: 2470-9468
DOI: https://doi.org/10.1126/sciimmunol.aat0297
Abstract
Lymphocytes recirculate continuously between the blood and lymphoid organs, a process that is of fundamental importance for proper functioning of the immune system. The molecular mechanisms underlying lymphocyte trafficking to the spleen remain an enigma. Here, we show that lymphocytes enter the spleen preferentially from vessels in the red pulp rather than the marginal sinus or the vasculature in the white pulp. Ex vivo adhesion assays in mice and humans, together with genetic ablation of Clever-1 in mice, indicate that CD8(+) T cell and B220(+) B cell homing to the spleen via the red pulp is Clever-1 dependent. Moreover, absence of Clever-1 leads to down-regulation of the B cell attractant chemokine, CXCL13, on spleen endothelium. CXCL13 is known to guide B cell trafficking to lymphoid organs, and its lack may contribute to the observed decrease in B cell trafficking into the spleen as well. In summary, this study identifies Clever-1 as an important molecule controlling lymphocyte entry into the spleen, along with a critical role for the splenic red pulp in this regulated trafficking. Furthermore, the results demonstrate that location-specific homing-associated molecules guide lymphocyte entry into the spleen.
Lymphocytes recirculate continuously between the blood and lymphoid organs, a process that is of fundamental importance for proper functioning of the immune system. The molecular mechanisms underlying lymphocyte trafficking to the spleen remain an enigma. Here, we show that lymphocytes enter the spleen preferentially from vessels in the red pulp rather than the marginal sinus or the vasculature in the white pulp. Ex vivo adhesion assays in mice and humans, together with genetic ablation of Clever-1 in mice, indicate that CD8(+) T cell and B220(+) B cell homing to the spleen via the red pulp is Clever-1 dependent. Moreover, absence of Clever-1 leads to down-regulation of the B cell attractant chemokine, CXCL13, on spleen endothelium. CXCL13 is known to guide B cell trafficking to lymphoid organs, and its lack may contribute to the observed decrease in B cell trafficking into the spleen as well. In summary, this study identifies Clever-1 as an important molecule controlling lymphocyte entry into the spleen, along with a critical role for the splenic red pulp in this regulated trafficking. Furthermore, the results demonstrate that location-specific homing-associated molecules guide lymphocyte entry into the spleen.
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