Impaired regulatory T cell-dendritic cell interactions contribute to autoimmunity in leukocyte adhesion deficiency type-1.

JCI insight(2022)

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摘要
Leukocyte Adhesion Deficiency Type-1 (LAD-1) is a rare disease resulting from mutations in the gene encoding for the common β-chain of the ß2 integrin family (CD18). The most prominent clinical symptoms are profound leukocytosis and high susceptibility to infections. At the same time, LAD-1 patients are prone to develop autoimmune diseases, but the molecular and cellular mechanisms that result in coexisting immunodeficiency and autoimmunity are still unresolved. CD4+FOXP3+ regulatory T cells (Treg) are known for their essential role in preventing autoimmunity. To understand the role of Treg in LAD-1 development and manifestation of autoimmunity we generated mice specifically lacking CD18 on Treg (CD18Foxp3), resulting in defective LFA-1 expression. Here we demonstrate a crucial role of LFA-1 on Treg to maintain immune homeostasis by modifying T cell - dendritic cell (DC) interactions and CD4+ T cell activation. Treg-specific CD18 deletion did not impair Treg migration into extra-lymphatic organs but resulted in shorter interactions of Treg with DC. In vivo, CD18Foxp3 mice developed spontaneous hyperplasia in lymphatic organs, and diffuse inflammation of the skin and in multiple internal organs. Thus, LFA-1 on Treg is required for the maintenance of immune homeostasis.
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关键词
Autoimmune diseases,Autoimmunity,T cells
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