Efficient homing of T cells via afferent lymphatics requires mechanical arrest and integrin-supported chemokine guidance
Open accessAbstract
Little is known regarding lymph node (LN)-homing of immune cells via afferent lymphatics. Here, we show, using a photo-convertible Dendra-2 reporter, that recently activated CD4 T cells enter downstream LNs via afferent lymphatics at high frequencies. Intra-lymphatic immune cell transfer and live imaging data further show that activated T cells come to an instantaneous arrest mediated passively by the mechanical 3D-sieve barrier of the LN subcapsular sinus (SCS). Arrested T cells subsequently migrate randomly on the sinus floor independent of both chemokines and integrins. However, chemokine receptors are imperative for guiding cells out of the SCS, and for their subsequent directional translocation towards the T cell zone. By contrast, integrins are dispensable for LN homing, yet still contribute by increasing the dwell time within the SCS and by potentially enhancing T cell sensing of chemokine gradients. Together, these findings provide fundamental insights into mechanisms that control homing of lymph-derived immune cells.
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Larger cells such as DCs, macrophages, and activated T cells gain access to the lymph node from the SCS.
“By contrast, larger cells such as DCs, macrophages, and activated T cells gain access to the lymph node from the SCS (92–94).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [94]
The Introduction (page unavailable) says DCs enter the lymph-node parenchyma through the SCS floor, and the Results section on CD4 T-cell movement (page unavailable) describes activated T cells crossing that floor. The paper mentions subcapsular macrophages but does not say that macrophages gain access to the lymph node from the SCS. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAfter entry into the lymph node, access of all immunocytes to their respective locations depends upon CCR7 and CCL21.
“After entry into the lymph node, access of all immunocytes to their respective locations depends upon CCR7 and CCL21 (92, 94).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [94]
The Results section (‘CCR7 is a major homing receptor for activated CD4 T cells’; page unavailable) shows that CCR7 helps lymph-derived activated CD4 T cells move from the subcapsular sinus toward the T-cell zone. The Discussion (page unavailable) relates that movement to a previously described CCL21 gradient. The paper does not establish that access to their respective locations depends on both CCR7 and CCL21 for all immunocytes. (LLM, conf=0.88)
Experimental — accuracy not yet measuredEntry of DCs and activated T cells from the SCS to the lymph node appears to be independent of integrins even under inflammatory conditions.
“However, in contrast to their entry into initial LVs, entry of DCs and activated T cells from the SCS to the lymph node appears to be independent of integrins even under inflammatory conditions (92, 94).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [94]
The Discussion reports that integrin-deficient DCs homed to and positioned within draining lymph nodes, supporting the DC portion. But it also states that fewer activated T cells lacking integrins or Talin1 entered the lymph-node parenchyma, so their entry was not integrin-independent. The Results examine SCS structure in inflamed nodes but do not establish integrin-independent entry under inflammatory conditions. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSmall resting T cells pass from the SCS to medullary lymphatic sinuses and gain access to the lymph node at this site.
“From the SCS, small resting T cells pass to medullary lymphatic sinuses and gain access to the lymph node at this site (92–94).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [94]
Transmigration of DCs and activated T cells across the SCS into the lymph node parenchyma is dependent on CCR7.
“Transmigration of DCs and activated T cells across the SCS into the lymph node parenchyma is also dependent on CCR7 (92, 94).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [94]
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- Authors
- Martens, R., Permanyer, M., Werth, K., Yu, K., Braun, A., Halle, O., Halle, S., Patzer, G. E., Bošnjak, B., Kiefer, F., Janssen, A., Friedrichsen, M., Poetzsch, J., Kohli, K., Lueder, Y., Gutierrez Jauregui, R., Eckert, N., Worbs, T., Galla, M., & Förster, R.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- Max Planck Institute for Molecular Biomedicine (DE)
- Corresponding author
- Förster, Reinhold
- ORCID
- Venue
- Nature Communications
- Published
- 2020-02-28
- Volume
- 11
- Issue
- 1
- Pages
- 1114-1114
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7048855
- OpenAlex
- W3009980117
- Cited by
- 55
- References
- 70
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 9 · 2021: 17 · 2020: 7
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Boehringer Ingelheim Fonds
- Deutsche Forschungsgemeinschaft (SFB-738, FO 334/5-1, SFB738-B5, SFB 900, EXC2155, SFB900‐B1, 39087428, Project ID39087428)
- Medizinischen Hochschule Hannover (SFB738)
- RWTH Aachen University
- FP7 Ideas: European Research Council (322645)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- lymph node homing, afferent lymphatics, CD4+ T cells, subcapsular sinus, integrins, chemokine receptors, chemokine gradients, T cell zone
- MeSH terms
- Animals, Cell Movement, Endothelium, Lymphatic, Lymph, Lymph Nodes, Lymphocyte Activation, CD4-Positive T-Lymphocytes, Integrins, Receptors, Lymphocyte Homing, Chemokines, Receptors, Chemokine, Mice
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