Impact of immune-metabolic interactions on age-related thymic demise and T cell senescence

详细信息    查看全文

• 作者：Vishwa Deep Dixit ; ^{Vishwa.Dixit@pbrc.edu}
• 关键词：Inflammation ; T cells ; Inflammasome ; NLRP3 ; CDR3 ; Aging ; Adipocytes ; Macrophages ; Pycard ; IL-1¦Â ; Caspase-1 ; ASC ; Free cholesterol ; Ceramide ; Fatty acids ; IL-7 ; Epithelial cell ; IL-18 ; Apoptosis ; Stem cells ; Bone marrow ; Cancer ; Fatty acids
• 刊名：Seminars in Immunology
• 出版年：2012
• 出版时间：October, 2012
• 年：2012
• 卷：24
• 期：5
• 页码：321-330
• 全文大小：1563 K

文摘

Emerging evidence indicates that the immune and metabolic interactions control several aspects of the aging process and associated chronic diseases. Among several sites of immune-metabolic interactions, thymic demise represents a particularly puzzling phenomenon because even in metabolically healthy middle-aged individuals the majority of thymic space is replaced with ectopic lipids. The new T cell specificities can only be generated in a functional thymus and, peripheral proliferation of pre-existing T cell clones provides limited immune-vigilance in the elderly. Therefore, it is hypothesized that the strategies that enhance thymic-lymphopoiesis may extend healthspan. Recent data suggest that byproducts of thymic fatty acids and lipids result in accumulation of ¡®lipotoxic DAMPs¡¯ (damage associated molecular patterns), which triggers the innate immune-sensing mechanism like inflammasome activation which links aging to thymic demise. The immune-metabolic interaction within the aging thymus produces a local pro-inflammatory state that directly compromises the thymic stromal microenvironment, thymic-lymphopoiesis and serves a precursor of systemic immune-dysregulation in the elderly. New evidence also suggests that ectopic thymic adipocytes may develop from specific intrathymic stromal cell precursors instead of a passive process that is simply a consequence of thymic lymphopenia. Thus the complex bidirectional interactions between metabolic and immune systems may link aging to health, T cell senescence, and associated diseases. This review discusses the immune-metabolic mechanisms during aging - with implications for developing future therapeutic strategies for living well beyond the expected.