Regulation of lymph node vascular growth by dendritic cells

Section: Immunosuppressive Roles Of Vegf-amentioning

confidence: 83%

B Cell-Derived Vascular Endothelial Growth Factor A Promotes Lymphangiogenesis and High Endothelial Venule Expansion in Lymph Nodes

Shrestha

Hashiguchi

Ito

et al. 2010

“…In the steady state, as much as 50% of recirculating lymphocytes passing through an LN exit through the efferent lymph (5). During inflammation, LN activation triggers remodeling of high endothelial venules (HEVs) to increase lymphocyte entry by manyfold (11,12). Undesirable situations, including LN hypertrophy and hyperactivation, which are often associated with autoimmune and chronic inflammatory diseases, may arise if these lymphocytes fail to leave the inflamed LNs in a timely manner.…”

Section: Discussionmentioning

confidence: 99%

“…However, recent studies indicated that plasticity in LN structural organization continues to exist throughout life, particularly during inflammation and infection (8,9). Reorganization of LN microanatomy during inflammation is characterized by the remodeling and expansion of key LN stromal cells, including lymphatic endothelial cells (LECs) (10), blood endothelial cells (BECs) (11,12), and fibroblastic reticular cells (FRCs) (13,14). Importantly, increasing evidence reveal the immunological significance of the remodeling of these stromal elements.…”

mentioning

confidence: 99%

Expansion of Cortical and Medullary Sinuses Restrains Lymph Node Hypertrophy during Prolonged Inflammation

Tan

Yeo

Wong

et al. 2012

During inflammation, accumulation of immune cells in activated lymph nodes (LNs), coupled with a transient shutdown in lymphocyte exit, results in dramatic cellular expansion. Counter-regulatory measures to restrain LN expansion must exist and may include re-establishment of lymphocyte egress to steady-state levels. Indeed, we show in a murine model that egress of lymphocytes from LNs was returned to steady-state levels during prolonged inflammation following initial retention. This restoration in lymphocyte egress was supported by a preferential expansion of cortical and medullary sinuses during late inflammation. Cortical and medullary sinus remodeling during late inflammation was dependent on temporal and spatial changes in vascular endothelial growth factor-A distribution. Specifically, its expression was restricted to the subcapsular space of the LN during early inflammation, whereas its expression was concentrated in the paracortical and medullary regions of the LN at later stages. We next showed that this process was mostly driven by the synergistic cross-talk between fibroblastic reticular cells and interstitial flow. Our data shed new light on the biological significance of LN lymphangiogenesis during prolonged inflammation and further underscore the collaborative roles of stromal cells, immune cells, and interstitial flow in modulating LN plasticity and function.

“…In addition, lymphotoxin signaling may also indirectly affect FRC turnover, because LTbR blockade severely attenuated BEC expansion in LTbR-Ig-treated mice. It is noteworthy that LTbR plays an important role in remodeling (28)(29)(30) and in the functional maintenance (24) of high endothelial venules (HEVs). Long-term LTbRIg treatment causes a loss of HEV phenotype (24), resulting in the impaired recruitment of lymphocytes into reactive LNs during the ongoing immune response.…”

Section: Discussionmentioning

confidence: 99%

Lymph Node Stromal Cells Negatively Regulate Antigen-Specific CD4+ T Cell Responses

Abe

Shichino

Ueha

et al. 2014

Lymph node (LN) stromal cells (LNSCs) form the functional structure of LNs and play an important role in lymphocyte survival and the maintenance of immune tolerance. Despite their broad spectrum of function, little is known about LNSC responses during microbial infection. In this study, we demonstrate that LNSC subsets display distinct kinetics following vaccinia virus infection. In particular, compared with the expansion of other LNSC subsets and the total LN cell population, the expansion of fibroblastic reticular cells (FRCs) was delayed and sustained by noncirculating progenitor cells. Notably, newly generated FRCs were preferentially located in perivascular areas. Viral clearance in reactive LNs preceded the onset of FRC expansion, raising the possibility that viral infection in LNs may have a negative impact on the differentiation of FRCs. We also found that MHC class II expression was upregulated in all LNSC subsets until day 10 postinfection. Genetic ablation of radioresistant stromal cell–mediated Ag presentation resulted in slower contraction of Ag-specific CD4+ T cells. We propose that activated LNSCs acquire enhanced Ag-presentation capacity, serving as an extrinsic brake system for CD4+ T cell responses. Disrupted function and homeostasis of LNSCs may contribute to immune deregulation in the context of chronic viral infection, autoimmunity, and graft-versus-host disease.