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Local innervation modulates lymph node cellularity
Author(s) -
Chen Chien Sin,
Ince Louise,
Juan Alba,
Hergenhan Sophia,
He Wenyan,
Druzd David,
Kraus Kerstin,
Scheiermann Christoph
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.358.3
Subject(s) - lymph , lymph node , germinal center , medicine , immune system , chemokine , lymphatic system , pathology , ccl19 , b cell , immunology , antibody , chemokine receptor
The sympathetic nervous system has been shown to modulate systemic and local immune responses but the function and the mechanism of nerve‐driven immune regulation remain largely unclear. Using surgical approaches, we ablated neural projections innervating peripheral lymph nodes and observed strong alterations in leukocyte populations and the local microenvironment. One week after unilateral transection of nerves, popliteal lymph nodes (popLNs) were found to be dramatically enlarged on the deneverated side compared to the sham‐operated lateral control side and remained high for the entire four week observation period. Nodal expansion was largely due to increased overall numbers in B and T lymphocytes. However, also strong increases in key microenvironmental cell types were observed including higher numbers of vascular and lymphatic endothelial cells and fibroblastic reticular cells. Two weeks after surgery, increased TNF‐α and interleukin‐4 levels were observed in denervated popLNs, along with a reduction in levels of the chemotactic molecule CCL19, without changes in other investigated cytokines and chemokines. Multiple germinal centers with pronounced proliferation of B cells were detected in denervated popLNs as assessed by immunofluorescence staining for Ki67. To selectively abolish sympathetic input to lymph nodes, we performed a unilateral superior cervical ganglionectomy (SCGx), and also found more germinal centers in sympathectomized superficial parotid LNs. These results indicate that direct sympathetic innervation can regulate lymph node cellularity. Support or Funding Information Funded by the German Research Foundation (Emmy Noether SCHE 1645/2‐1 and SFB914 projects B09 and Z03) and the European Research Council (CIRCODE, 635872)