Tertiary Lymphoid Structures: Autoimmunity Goes Local

Abstract

Tertiary lymphoid structures (TLS) are frequently observed in target organs of autoimmune diseases. TLS present features of secondary lymphoid organs such as segregated T and B cell zones, presence of follicular dendritic cell networks, high endothelial venules and specialized lymphoid fibroblasts and display the mechanisms to support local adaptive immune responses toward locally displayed antigens. TLS detection in the tissue is often associated with poor prognosis of disease, auto-antibody production and malignancy development. This review focuses on the contribution of TLS toward the persistence of the inflammatory drive, the survival of autoreactive lymphocyte clones and post-translational modifications, responsible for the pathogenicity of locally formed autoantibodies, during autoimmune disease development.

Extracellular vesicles derived from injured vascular tissue promote the formation of tertiary lymphoid structures in vascular allografts

“…Having shown increased allograft IL‐17 expression in allograft recipients injected with ApoExo, and taking into consideration previous work suggesting a central role for T helper 17 (Th17) cells in TLS neogenesis, we used flow cytometry analysis to evaluate the presence of Th17 cells within the allograft infiltrate. Although immunohistochemistry demonstrated a significant enhancement of infiltrating CD3 + T cells in allografts from mice injected with ApoExo compared to those injected with the vehicle (Figure E), flow cytometry analysis showed that the number of allograft infiltrating CD3 + TCRβ + T cells remained low upon injection of ApoExo compared to mice injected with vehicle (Figure A).…”

“…Gamma delta T (γδT) cells are unconventional T cells operating at the interface of innate and adaptive immunity, and are known to produce high levels of IL‐17 . They have also been implicated in the generation of TLS . The number of allograft‐infiltrating CD3 + TCR gamma (TCRγ) + T cells was significantly higher in mice injected with ApoExo compared to those injected with the vehicle (Figure D).…”

“…19 They have also been implicated in the generation of TLS. 1 The number of allograft-infiltrating CD3 + TCR gamma (TCRγ) + T cells was significantly higher in mice injected with ApoExo compared to those injected with the vehicle ( Figure 3D). ApoExo injection also increased the percentage of γδT cells within the CD3 + allograft infiltrate ( Figure 3E,F).…”

“…Tertiary lymphoid structures (TLS) are associated with chronic infections, chronically rejected organ transplants and autoimmune conditions . TLS are nodular structures comprised of segregated T and B cells reminiscent of secondary lymphoid organs.…”

Beyond antibodies: B cells in Hidradenitis Suppurativa: Bystanders, contributors or therapeutic targets?

“…TLOs are abnormal lymphoid‐like structures which form in peripheral tissues in the setting of chronic inflammation, infection and transplant rejection and have been identified in HS [1,18] . TLOs are essential sites of autoreactive B‐cell development and survival [19] . IL‐17+ T‐cells have been shown as essential to the development of TLOs in murine and human models of RA and SLE, [20] with IL‐17, IL‐22 and IL‐27 all impacting TLO formation in animal models [21] .…”