Biological mechanisms of ectopic lymphoid structure formation and their pathophysiological significance.

Ectopic lymphoid structures (ELS) or tertiary lymphoid organs are structures with the organization similar to the one of secondary lymphoid organs, formed in non-lymphoid tissues. They are considered to be an important site for the lymphocytic physiological and pathological role in conditions such are chronic infections, autoimmune diseases, cancer, and allograft rejection. Although similar to the secondary lymphoid tissues, the initiation of ELS formation is not preprogramed and requires chronic inflammation, expression of homeostatic chemokines, and lymphotoxin beta receptor activation. Importantly, while ELS formation may be considered beneficiary in antimicrobial and antitumor immunity, the persistence of these active lymphoid structures within the tissue increase the chance for development of autoimmunity and lymphoma. This paper is providing an overview of biological mechanisms involved in ELS formation, as well as the overview of the pathophysiological role of these structures. In addition, the paper discusses the possibility to therapeutically target ELS formation, bearing in mind their bivalent nature and role in different pathophysiological conditions.