The roles of tertiary lymphoid structures in chronic diseases.

Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues that drive antigen-specific immune responses at sites of chronic inflammation. Unlike secondary lymphoid organs such as lymph nodes, TLSs lack capsules and have their own unique characteristics and functions. The presumed influence of TLSs on the disease course has led to widespread interest in obtaining a better understanding of their biology and function. Studies using single-cell analyses have suggested heterogeneity in TLS composition and phenotype, and consequently, functional correlates with disease progression are sometimes conflicting. The presence of TLSs correlates with a favourable disease course in cancer and infection. Conversely, in autoimmune diseases and chronic age-related inflammatory diseases including chronic kidney disease, the presence of TLSs is associated with a more severe disease course. However, the detailed mechanisms that underlie these clinical associations are not fully understood. To what extent the mechanisms of TLS development and maturation are shared across organs and diseases is also still obscure. Improved understanding of TLS development and function at the cellular and molecular levels may enable the exploitation of these structures to improve therapies for chronic diseases, including chronic kidney disease. Here, the authors discuss tertiary lymphoid structure (TLS) development, maintenance and function, with a focus on the roles of TLSs in autoimmune disease, cancer, infection and chronic age-related inflammatory diseases. They also discuss the clinical implications of TLSs in various tissues and diseases. Key points: Tertiary lymphoid structures (TLSs) are organized lymphoid aggregates that develop in perivascular areas in response to disturbed tissue homeostasis. TLSs serve as local immune niches to promote adaptive immunity; their unencapsulated structure enables direct exposure to diverse stimuli from an inflamed environment. The development of TLSs in different organs involves common mechanisms that are presumably regulated by tissue-specific cues. The presence of TLSs correlates with a favourable disease course in many types of cancer and infection. In autoimmunity, chronic inflammation and ageing, the presence of TLSs correlates with pathological conditions and a more severe disease course. Functional characterization of TLSs in human diseases and the development of interventions to induce or reduce TLSs could lead to promising therapeutic avenues. [ABSTRACT FROM AUTHOR]