Butyrophilin 2a2 (Btn2a2) expression on thymic epithelial cells promotes central T cell tolerance and prevents autoimmune disease

Frech, Michael; Danzer, Heike; Uchil, Pooja; Azizov, Vugar; Schmid, Eva; Schälter, Fabian; Dürholz, Kerstin; Mauro, Daniele; Rauber, Simon; Muñoz, Luis; Taher, Leila; Ciccia, Francesco; Schober, Kilian; Irla, Magali; Sarter, Kerstin; Schett, Georg; Zaiss, Mario M.

doi:10.1016/j.jaut.2023.103071

Cited by 1 publication

(2 citation statements)

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“…Among these, the MHCII-TCR interaction between thymic APCs and thymocytes, referred to as thymic crosstalk, influences mature mTEC development, TRA expression and immune tolerance induction, leading to autoimmune phenotypes if abrogated ( 22 , 23 , 136 ). Moreover, the butyrophilin surface receptor Btn2a2 expressed on thymic epithelial cells is important for central T cell tolerance induction ( 137 , 138 ). Btn2a2-deficient mice showed enhanced effector CD4 + and CD8 + T cell responses, impaired CD4 + regulatory T cell induction, potentiated antitumor responses, and exacerbated experimental autoimmune encephalomyelitis ( 137 ).…”

Section: Central Immune Tolerancementioning

confidence: 99%

“…Btn2a2-deficient mice showed enhanced effector CD4 + and CD8 + T cell responses, impaired CD4 + regulatory T cell induction, potentiated antitumor responses, and exacerbated experimental autoimmune encephalomyelitis ( 137 ). While another study reported increased TCR signaling and CD5 levels for developing thymocytes in Btn2a2-deficient mice with otherwise unchanged TEC compartments and thymic T cell populations ( 138 ).…”

Section: Central Immune Tolerancementioning

confidence: 99%

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Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis

Shirafkan,

Hensel,

Rattay

2024

Front. Immunol.

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The intricate balance of immune reactions towards invading pathogens and immune tolerance towards self is pivotal in preventing autoimmune diseases, with the thymus playing a central role in establishing and maintaining this equilibrium. The induction of central immune tolerance in the thymus involves the elimination of self-reactive T cells, a mechanism essential for averting autoimmunity. Disruption of the thymic T cell selection mechanisms can lead to the development of autoimmune diseases. In the dynamic microenvironment of the thymus, T cell migration and interactions with thymic stromal cells are critical for the selection processes that ensure self-tolerance. Thymic epithelial cells are particularly significant in this context, presenting self-antigens and inducing the negative selection of autoreactive T cells. Further, the synergistic roles of thymic fibroblasts, B cells, and dendritic cells in antigen presentation, selection and the development of regulatory T cells are pivotal in maintaining immune responses tightly regulated. This review article collates these insights, offering a comprehensive examination of the multifaceted role of thymic tissue homeostasis in the establishment of immune tolerance and its implications in the prevention of autoimmune diseases. Additionally, the developmental pathways of the thymus are explored, highlighting how genetic aberrations can disrupt thymic architecture and function, leading to autoimmune conditions. The impact of infections on immune tolerance is another critical area, with pathogens potentially triggering autoimmunity by altering thymic homeostasis. Overall, this review underscores the integral role of thymic tissue homeostasis in the prevention of autoimmune diseases, discussing insights into potential therapeutic strategies and examining putative avenues for future research on developing thymic-based therapies in treating and preventing autoimmune conditions.

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