Abstract
Fibroblastic reticular cells (FRCs), usually found and isolated from the T cell zone of lymph nodes, have recently been described as much more than simple structural cells. Originally, these cells were described to form a conduit system called the “reticular fiber network” and for being responsible for transferring the lymph fluid drained from tissues through afferent lymphatic vessels to the T cell zone. However, nowadays, these cells are described as being capable of secreting several cytokines and chemokines and possessing the ability to interfere with the immune response, improving it, and also controlling lymphocyte proliferation. Here, we performed a systematic review of the several methods employed to investigate the mechanisms used by fibroblastic reticular cells to control the immune response, as well as their ability in determining the fate of T cells. We searched articles indexed and published in the last five years, between 2016 and 2020, in PubMed, Scopus, and Cochrane, following the PRISMA guidelines. We found 175 articles published in the literature using our searching strategies, but only 24 articles fulfilled our inclusion criteria and are discussed here. Other articles important in the built knowledge of FRCs were included in the introduction and discussion. The studies selected for this review used different strategies in order to access the contribution of FRCs to different mechanisms involved in the immune response: 21% evaluated viral infection in this context, 13% used a model of autoimmunity, 8% used a model of GvHD or cancer, 4% used a model of Ischemic-reperfusion injury (IRI). Another four studies just targeted a particular signaling pathway, such as MHC II expression, FRC microvesicles, FRC secretion of IL-15, FRC network, or ablation of the lysophosphatidic acid (LPA)-producing ectoenzyme autotaxin. In conclusion, our review shows the strategies used by several studies to isolate and culture fibroblastic reticular cells, the models chosen by each one, and dissects their main findings and implications in homeostasis and disease.
Highlights
Lymph node structural organization is reported to be governed by the stromal cells [1]
We searched for articles indexed in the Pubmed, Scopus, and Cochrane libraries published between 2016 and 2020, and a total of 175 articles were identified in these databases
After the Pubmed screening, 11 articles were not included due to the lack of analysis on Fibroblast reticular cells (FRCs)’ impact on T cell function, and 17 full-text articles were assessed for eligibility
Summary
Lymph node structural organization is reported to be governed by the stromal cells [1]. FRCs are described to be organized in a conduit system called the “reticular fiber network”, responsible for transferring antigens from tissue to T cell zones in LNs and for controlling the conduit matrix deposition during lymph node expansion [3,4]. Their ability for cytokine and chemokine production has been demonstrated in several studies [2,5,6], and their relevant multifunctional roles and multiple subsets have been previously defined [7]. Other cells previously known as structural cells, such as epithelium, endothelium, and fibroblasts, have been implicated as players in the immune response [17]
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