Kidney fibrosis is a well-known consequence of repeated ischaemia–reperfusion injury (IRI), but what happens to the draining lymph node? Reza Abdi and his team now report that the kidney lymph node not only has an important role in lymphocyte activation after IRI but also undergoes fibrotic changes.
“Our early work showed that the kidney lymph node undergoes a massive microstructural transformation following IRI,” remarks Abdi. As fibroblastic reticular cells (FRCs) have a key role in the maintenance of the lymph node structural framework, which facilitates the trafficking of immune cells and antigens, the researchers focused their recent study on the impact of IRI on FRCs and lymph node architecture.
Their new findings show that following kidney IRI, both T cells and FRCs actively proliferate in the draining lymph node. This proliferation is accompanied by increased collagen deposition, macrophage infiltration and expansion of high endothelial venules. Expression of the profibrotic genes encoding α-smooth muscle actin and fibronectin also increases in the kidney lymph node after IRI.
Furthermore, the researchers demonstrate that in the setting of repeated IRI, both the kidney and lymph node become increasingly fibrotic as they accumulate collagen I and fibronectin. In contrast to the expansion observed in acute IRI, FRC density in the lymph node decreases following repeated IRI owing to senescence of these cells. In the acute setting, FRC depletion reduced T cell activation in the lymph node and kidney injury. However, in the chronic setting of recurrent IRI, transfer of exogenous FRCs, which homed to the lymph node draining the ischaemic kidney, ameliorated renal fibrosis and restored lymph node microarchitecture.
“I believe that the reason why we have not been able to target organ fibrosis effectively is that we have forgotten about the critical role of the draining lymph nodes in regulating organ inflammation,” comments Abdi. “To control organ fibrosis we may need to target lymph node fibrosis at the same time.”
Maarouf, O. H. et al. Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing. JCI Insight 3, e120546 (2018)
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Wang, M. Lymph node fibrosis after ischaemic injury. Nat Rev Nephrol 14, 599 (2018). https://doi.org/10.1038/s41581-018-0050-2