Developmental Disorders of the Lymphatics

An information blog for disorders of the lymphatics. For all articles, please click on "Archives" - Due to spammers, I will no longer allow comments, sorry.

Monday, October 09, 2006

Lymphoid Neogenesis

Is defective lymphatic drainage a trigger for lymphoid neogenesis?
Thaunat O,
Kerjaschki D,
Nicoletti A.

Universite Pierre et Marie Curie - Paris 6, INSERM UMR S 681, Centre de recherche des Cordeliers - 75006, Paris, France.

October 2006

The progressive organization of cellular infiltrates into functional ectopic germinal centers (i.e. lymphoid neogenesis) has been recently evidenced in various chronic inflammatory diseases. Failure of the immune system to eradicate the targeted antigen(s) is a shared feature of all of the pathological situations associated with lymphoid neogenesis. Although necessary, inability of the immune system to eradicate the antigen(s) seems insufficient to trigger lymphoid neogenesis by itself. We propose that both defective lymphatic drainage of the inflamed tissue and enduring local antigenic stimulation are the crucial triggers of the cascade of events leading to lymphoid neogenesis. In turn, ectopic germinal centers prevent the restoration of lymph outflow by diverting inflammation-dependent lymphangiogenesis. Antigens and immune effectors are rerouted towards the neoformed ectopic lymphoid structures. A self-perpetuating feedback loop, which further sustains the development of the local immune response, is now imposed.

PMID: 16920402 [PubMed - in process]

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Lymphoid neogenesis in chronic rejection: the murderer is in the house.

Curr Opin Immunol. 2006 Oct;18

Universite Pierre et Marie Curie-Paris 6, INSERM UMR S 681, Centre de recherche des Cordeliers, 15 rue de l'Ecole de Medecine, 75006 Paris, France.

Although chronic rejection is currently the main cause of long-term allograft failure, its pathogenesis remains elusive, hereby preventing the development of effective therapy. Recent advances in the comprehension of the pathophysiology of chronic inflammatory diseases could shed new light on the pathogenesis of chronic rejection.

Lymphoid neogenesis is a mechanism responsible for the progressive organization of chronic inflammatory infiltrates into functional ectopic germinal centers, and has been evidenced recently in various pathological situations sharing a common feature: the failure of the immune response to eradicate the targeted antigen(s). Chronic rejection is such a situation as it results from a sustained alloimmune response against the donor's antigens that are constantly replenished by the grafted tissue.

Accordingly, functional ectopic germinal centers develop within chronically rejected organs. This implies that, during chronic rejection, graft is at the same time the target and the site of elicitation of the alloimmune response.

PMID: 16879953 [PubMed - as supplied by publisher]

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Lymphoid neogenesis in chronic inflammatory diseases.

Nat Rev Immunol. 2006 Mar

Department of Cell Biology and Neuroscience, Istituto Superiore di Sanita, Rome, Italy.

The frequent observation of organized lymphoid structures that resemble secondary lymphoid organs in tissues that are targeted by chronic inflammatory processes, such as autoimmunity and infection, has indicated that lymphoid neogenesis might have a role in maintaining immune responses against persistent antigens. In this Review, we discuss recent progress in several aspects of lymphoid neogenesis, focusing on the similarities with lymphoid tissue development, the mechanisms of induction, functional competence and pathophysiological significance. As more information on these issues becomes available, a better understanding of the role of lymphoid neogenesis in promoting chronic inflammation might eventually lead to new strategies to target immunopathological processes.

PMID: 16498451 [PubMed - indexed for MEDLINE]

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Lymphoid organ development: from ontogeny to neogenesis.

Nat Immunol. 2006 Apr

Drayton DL,
Liao S,
Mounzer RH,
Ruddle NH.

Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8034, USA.

The development of lymphoid organs can be viewed as a continuum. At one end are the 'canonical' secondary lymphoid organs, including lymph nodes and spleen; at the other end are 'ectopic' or tertiary lymphoid organs, which are cellular accumulations arising during chronic inflammation by the process of lymphoid neogenesis. Secondary lymphoid organs are genetically 'preprogrammed' and 'prepatterned' during ontogeny, whereas tertiary lymphoid organs arise under environmental influences and are not restricted to specific developmental 'windows' or anatomic locations. Between these two boundaries are other types of lymphoid tissues that are less developmentally but more environmentally regulated, such as Peyer's patches, nasal-associated lymphoid tissue, bronchial-associated lymphoid tissue and inducible bronchial-associated lymphoid tissue. Their regulation, functions and potential effects are discussed here.

PMID: 16550197 [PubMed - indexed for MEDLINE]