LFA-1/ICAM-1 Adhesion Pathway Mediates the Homeostatic Migration of Lymphocytes from Peripheral Tissues into Lymph Nodes through Lymphatic Vessels
Lymphocyte function-associated antigen-1 (LFA-1) and its endothelial ligand intercellular adhesion molecule-1 (ICAM-1) are important for the migration of lymphocytes from blood vessels into lymph nodes. However, it is largely unknown whether these molecules mediate the homeostatic migration of lymph...
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MDPI AG
2023-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/8/1194 |
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| author | Jia Guo Zeyu Xu Rachel C. Gunderson Baohui Xu Sara A. Michie |
| author_facet | Jia Guo Zeyu Xu Rachel C. Gunderson Baohui Xu Sara A. Michie |
| author_sort | Jia Guo |
| collection | DOAJ |
| description | Lymphocyte function-associated antigen-1 (LFA-1) and its endothelial ligand intercellular adhesion molecule-1 (ICAM-1) are important for the migration of lymphocytes from blood vessels into lymph nodes. However, it is largely unknown whether these molecules mediate the homeostatic migration of lymphocytes from peripheral tissues into lymph nodes through lymphatic vessels. In this study, we find that, in naive mice, ICAM-1 is expressed on the sinus endothelia of lymph nodes, but not on the lymphatic vessels of peripheral tissues. In in vivo lymphocyte migration assays, memory CD4<sup>+</sup> T cells migrated to lymph nodes from peripheral tissues much more efficiently than from blood vessels, as compared to naive CD4<sup>+</sup> T cells. Moreover, ICAM-1 deficiency in host mice significantly inhibited the migration of adoptively transferred wild-type donor lymphocytes from peripheral tissues, but not from blood vessels, into lymph nodes. The migration of LFA-1-deficient donor lymphocytes from peripheral tissues into the lymph nodes of wild-type host mice was also significantly reduced as compared to wild-type donor lymphocytes. Furthermore, the number of memory T cells in lymph nodes was significantly reduced in the absence of ICAM-1 or LFA-1. Thus, our study extends the functions of the LFA-1/ICAM-1 adhesion pathway, indicating its novel role in controlling the homeostatic migration of lymphocytes from peripheral tissues into lymph nodes and maintaining memory T cellularity in lymph nodes. |
| first_indexed | 2024-03-11T00:05:21Z |
| format | Article |
| id | doaj.art-5a0342ac9ed44955b31c94a6171df62e |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T00:05:21Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-5a0342ac9ed44955b31c94a6171df62e2023-11-19T00:23:33ZengMDPI AGBiomolecules2218-273X2023-07-01138119410.3390/biom13081194LFA-1/ICAM-1 Adhesion Pathway Mediates the Homeostatic Migration of Lymphocytes from Peripheral Tissues into Lymph Nodes through Lymphatic VesselsJia Guo0Zeyu Xu1Rachel C. Gunderson2Baohui Xu3Sara A. Michie4Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USALymphocyte function-associated antigen-1 (LFA-1) and its endothelial ligand intercellular adhesion molecule-1 (ICAM-1) are important for the migration of lymphocytes from blood vessels into lymph nodes. However, it is largely unknown whether these molecules mediate the homeostatic migration of lymphocytes from peripheral tissues into lymph nodes through lymphatic vessels. In this study, we find that, in naive mice, ICAM-1 is expressed on the sinus endothelia of lymph nodes, but not on the lymphatic vessels of peripheral tissues. In in vivo lymphocyte migration assays, memory CD4<sup>+</sup> T cells migrated to lymph nodes from peripheral tissues much more efficiently than from blood vessels, as compared to naive CD4<sup>+</sup> T cells. Moreover, ICAM-1 deficiency in host mice significantly inhibited the migration of adoptively transferred wild-type donor lymphocytes from peripheral tissues, but not from blood vessels, into lymph nodes. The migration of LFA-1-deficient donor lymphocytes from peripheral tissues into the lymph nodes of wild-type host mice was also significantly reduced as compared to wild-type donor lymphocytes. Furthermore, the number of memory T cells in lymph nodes was significantly reduced in the absence of ICAM-1 or LFA-1. Thus, our study extends the functions of the LFA-1/ICAM-1 adhesion pathway, indicating its novel role in controlling the homeostatic migration of lymphocytes from peripheral tissues into lymph nodes and maintaining memory T cellularity in lymph nodes.https://www.mdpi.com/2218-273X/13/8/1194leukocyte function-associated antigen-1intercellular adhesion molecule-1lymphocytesmigrationlymphatics |
| spellingShingle | Jia Guo Zeyu Xu Rachel C. Gunderson Baohui Xu Sara A. Michie LFA-1/ICAM-1 Adhesion Pathway Mediates the Homeostatic Migration of Lymphocytes from Peripheral Tissues into Lymph Nodes through Lymphatic Vessels Biomolecules leukocyte function-associated antigen-1 intercellular adhesion molecule-1 lymphocytes migration lymphatics |
| title | LFA-1/ICAM-1 Adhesion Pathway Mediates the Homeostatic Migration of Lymphocytes from Peripheral Tissues into Lymph Nodes through Lymphatic Vessels |
| title_full | LFA-1/ICAM-1 Adhesion Pathway Mediates the Homeostatic Migration of Lymphocytes from Peripheral Tissues into Lymph Nodes through Lymphatic Vessels |
| title_fullStr | LFA-1/ICAM-1 Adhesion Pathway Mediates the Homeostatic Migration of Lymphocytes from Peripheral Tissues into Lymph Nodes through Lymphatic Vessels |
| title_full_unstemmed | LFA-1/ICAM-1 Adhesion Pathway Mediates the Homeostatic Migration of Lymphocytes from Peripheral Tissues into Lymph Nodes through Lymphatic Vessels |
| title_short | LFA-1/ICAM-1 Adhesion Pathway Mediates the Homeostatic Migration of Lymphocytes from Peripheral Tissues into Lymph Nodes through Lymphatic Vessels |
| title_sort | lfa 1 icam 1 adhesion pathway mediates the homeostatic migration of lymphocytes from peripheral tissues into lymph nodes through lymphatic vessels |
| topic | leukocyte function-associated antigen-1 intercellular adhesion molecule-1 lymphocytes migration lymphatics |
| url | https://www.mdpi.com/2218-273X/13/8/1194 |
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