Lymphatic Vessel‐independent Lymph Flow Pattern from the Peri‐nodal Adipose Tissue to the Lymph Node

Rationale Lymph nodes (LNs) anatomically are distributed along the lymphatic vessels to survey materials carried by the lymph flow. Adipose tissue is a reservoir of hormones, cytokines, metabolites that can regulate immune responses and cell homeostasis in the LNs. Although lymphatic vessel and LNs are always surrounded by adipose tissue, lymph or cell communication between the peri‐nonal adipose tissue and the LNs remains unclear. Objective We aimed to understand how lymph flows from the peri‐nodal adipose tissue to the LNs. Methods and Results Using high‐resolution, super‐resolution and 3D reconstruction images, we studied the lymph distribution pattern from the adipose tissue to and through the LN. We found that a subset of LN conduits that are initiated at the LN capsule (LNC conduits), connect the afferent subcapsular sinus (SCS) and efferent medullary sinus (MS) and facilitate rapid lymph flow through the LN parenchyma. Super‐resolution images showed the unprecedented heterogeneous flow patterns inside LNC conduits. Surprisingly, we found that the LN capsule and its associated LNC conduits connect to the collagen channels in the fat tissue and provide an additional route supports lymph flow from the peri‐nodal adipose tissue to the LN (Fat‐LNC conduits). The type of materials entering the Fat‐LN conduits is dictated by molecular size. Finally, small molecules can enter LN after the afferent lymphatic vessels are sutured. Conclusions The lymph distribution pattern suggests that Fat‐LNC conduit support lymphatic vessel‐independent lymph flow from peri‐nodal adipose tissue to the LN, which provide a “highway” for fat‐derived factors to regulate LN microenvironment. Support or Funding Information Dianne & Irving Kipnes Foundation, Natural Sciences and Engineering Research Council of Canada (NSERC RGPIN‐2015‐03641), Canadian Institute of Health Research (CIHR) to SL and Canada Foundation for Innovation to SL.