The development of lymphoid organs can be viewed as a continuum. At one end are the ‘canonical’ secondary lymphoid organs, including lymph nodes and. Abstract: The development of lymphoid organs can be viewed as a continuum. At one end are the ‘canonical’ secondary lymphoid organs, including lymph. Lymphoid organ development: from ontogeny to neogenesis. (English). 1 reference. stated in · Europe PubMed Central · PubMed ID · · retrieved.

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Our studies on high endothelial venules and lymphatic vessels elucidate developmental mechanisms and point the way towards treatment and prevention of chronic inflammation.

Lymphoid organ development: from ontogeny to neogenesis

Perhaps ontogehy occurs because memory cells leave developmnt tumor TLO via LVs, and the activated cells traffic throughout the body and seek out metastatic disease. Elucidation of LV regulatory mechanisms in TLOs will contribute to the development of therapies to either promote or inhibit their formation, but we must keep in mind that LVs may be beneficial or detrimental depending on their context.

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They study autoimmune diseases, the inflammatory stage neigenesis Type 1 diabetes mellitus, and experimental autoimmune encephalomyelitis EAE dveelopment, a model for multiple sclerosis. Cytokines, autoantigens, or infectious organisms can give rise to chronic cellular accumulations called “ectopic” or “tertiary lymphoid organs,” through a process termed lymphoid organ neogenesis.

Thus, the necessity for antigen transport to the TLO through an lymphoi LV system might not be necessary, and the LVs may not serve that function. The initial thin-walled vessels, called capillaries, progress to collecting vessels and then to larger vessels such as the thoracic duct.

TLOs likely function as local sites of antigen presentation and lymphocyte activation, including somatic hypermutation and class switching in B cells 31which suggests that they facilitate local antimicrobial responses as well as epitope spreading 3233 and autoimmune exacerbation. During low-dose, streptozotocin-induced pancreatic inflammation, there is a marked increase in macrophages in and around the islets.


Even though most of these elements are also present in TLOs 5the order in which they populate the TLO may differ from the precise temporal aspect of LNs. During ontogeny, LVs develop after the embryonic blood vessels have formed, sprouting from the cardinal vein Human and Translational Immunology Program. Tertiary lymphoid organs TLOs are accumulations of lymphoid cells in chronic inflammation that resemble LNs in their cellular content and organization, high endothelial venules, and lymphatic vessels LVs.

Thus, in this context, the LVs in tumor TLOs are beneficial, as they serve as an exit for activated lymphocytes. The presentation of self-antigen in LNs 19 that has been suggested as a mechanism for self-tolerance has not been investigated in TLOs and is an important area for future research. Since the high number of HEVs also correlates with reduced metastases, lymphoi need to consider that the response generated in the tumor is effective elsewhere.

Treatments that discourage LV development, such as inhibition of macrophages clodronatecytokines antibodies or receptor blockersand growth factors e. Go to JCI Insight.

Osteoclast precursors, which include cells with macrophage properties, participate in lymphangiogenesis in a model of TNF transgene— and serum-mediated RA Prox1 function is required for the development of the murine lymphatic system. This is only effective if the mice have already developed pancreatic TLOs Their intogeny in TLOs adds to the complexity and excitement in this emerging field. Showing of references.

S1P is found in high concentrations in the blood and lymph, where lymphocytes express low levels of the receptor, S1PR1. Sign up for email alerts.

JCI – Lymphatic vessels and tertiary lymphoid organs

Engineering artificial TLOs may be of benefit in counteracting the effects of lymphedema. The key is to study TLOs in tissues that are amenable to these techniques, which will allow the evaluation of questions concerning LV insufficiency, memory, and plasticity in LVs in TLOs, and on a functional level, to determine whether valves and muscles occur in these vessels.


For example, in the non-obese diabetic NOD mouse model of type 1 diabetes mellitus T1DMinitial pancreatic infiltrates are characterized by HEV development and minimal islet destruction, whereas later stages demonstrate frank islet destruction and diabetes Fluid balance is a critical function of LVs in the body.

As noted above, lymphoid chemokines regulate trafficking of lymphocytes and DCs to and within LNs, and their expression 2030 is one criterion that defines TLOs.

A logical approach to inhibiting this spread would be the use of lymphangiogenesis inhibitors Lynphoid cells may be orgna at different times in various tissues. On the other hand, the presence of blood vessels and their nearby LVs in TLOs suggests that lymphangiogenesis in inflammation occurs by sprouting from existing LVs. First published March 3, – Version history. Epidemiology of Microbial Diseases. However, users may print, download, or email articles for individual use.

It has been suggested that TLOs differ from SLOs by the absence of a capsule; however, TLOs in a variety of chronic kidney diseases are in contact with a fibrous capsule TLO-associated LVs may also function in an efferent capacity by transporting activated lymphocytes to the periphery. Ongoing work to elucidate the function and molecular regulation of LVs in TLOs is providing insight into therapies for conditions as diverse as lymphedema, autoimmunity, and cancer.

Topics Discussed in This Paper. Finally, the influence of the local environment on the LVs in TLOs in different organs must be analyzed.