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Published on: January 7, 2019
Inflammatory cytokines IL-6 and TNF-α regulate lymphocyte trafficking through the local lymph node
Janet L-K Wee1, Deanne L V Greenwood, Xiaoyan Han
1Centre for Animal Biotechnology, Faculty of Veterinary Science, The University of Melbourne, Parkville, 3010 Victoria, Australia.
Insights
Cytokines like IL-6 and TNF-α regulate lymphocyte trafficking into lymph nodes. These cytokines induce a shutdown and recruitment response, crucial for immune cell interactions and immune response induction.
Area of Science:
- Immunology
- Cell Biology
- Physiology
Background:
- Lymphocyte trafficking is essential for immune surveillance and response.
- Steady-state lymphocyte flow through lymph nodes shifts to a bimodal pattern (shutdown/recruitment) upon stimulation.
- Cytokines, including TNF-α, are implicated in regulating this dynamic cell trafficking.
Purpose of the Study:
- To investigate the role of specific cytokines in regulating lymphocyte trafficking dynamics in vivo.
- To elucidate the mechanisms by which cytokines like IL-6 and TNF-α influence lymph node cell output.
Main Methods:
- Utilized an in vivo sheep lymphatic cannulation model.
- Cannulated prefemoral lymph nodes in sheep.
- Administered recombinant IL-6 and TNF-α subcutaneously into the draining area of cannulated nodes.
Main Results:
- Local injection of IL-6 directly stimulated the shutdown/recruitment response in lymph nodes.
- Local injection of TNF-α also induced shutdown/recruitment.
- Evidence suggests TNF-α may exert its effects indirectly, potentially via IL-6 induction.
Conclusions:
- IL-6 and TNF-α are key regulators of lymph node lymphocyte trafficking.
- The shutdown/recruitment pattern is cytokine-dependent and critical for immune cell interactions.
- TNF-α's regulatory role in lymphocyte trafficking may be mediated through IL-6.
Abstract:
Lymphocyte trafficking from blood to lymph and back is a tightly regulated process. Given appropriate stimuli, trafficking of cells through the lymph node changes from a 'steady-state' to a bimodal flow. Initially, a 'shutdown' phase occurs, leading to a dramatic reduction in efferent cell output. This is followed by a 'recruitment' phase whereby the efferent cell output becomes greatly elevated before returning to baseline levels. The shutdown/recruitment process is hypothesised to promote encounters between Ag-specific lymphocytes and APCs in an environment conducive to immune response induction. Cytokines, such as TNF-α have been shown to play an important role in regulating lymphocyte trafficking. Here, we unravel the role of cytokines in the regulation of cell trafficking using an in vivo sheep lymphatic cannulation model whereby the prefemoral lymph nodes were cannulated and recombinant cytokines were injected subcutaneously into the draining area of the cannulated node. We demonstrate that local injection of purified IL-6 or TNF-α stimulates shutdown/recruitment in the draining lymph node. While the effect of IL-6 appears to be direct, TNF-α may mediate shutdown/recruitment through IL-6.
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