T-Cell Aging-Associated Phenotypes in Autoimmune Disease

Frontiers in Aging

Tuantuan V. Zhao¹  Yuki Sato¹  Jorg J. Goronzy²  Cornelia M. Weyand² 

[1] Mayo Clinic Alix School of Medicine, College of Medicine and Science, Rochester, MN, United States;School of Medicine, Stanford University, Stanford, CA, United States;

关键词: immune aging;    autoimmune disease;    rheumatoid arthritis;    giant cell arteritis;    tissue invasiveness;    mitochondrial metabolism;   

DOI  :  10.3389/fragi.2022.867950

来源: DOAJ

【 摘 要 】

The aging process causes profound restructuring of the host immune system, typically associated with declining host protection against cancer and infection. In the case of T cells, aging leads to the accumulation of a diverse set of T-cell aging-associated phenotypes (TASP), some of which have been implicated in driving tissue inflammation in autoimmune diseases. T cell aging as a risk determinant for autoimmunity is exemplified in two classical autoimmune conditions: rheumatoid arthritis (RA), a disease predominantly affecting postmenopausal women, and giant cell arteritis (GCA), an inflammatory vasculopathy exclusively occurring during the 6th–9th decade of life. Pathogenic T cells in RA emerge as a consequence of premature immune aging. They have shortening and fragility of telomeric DNA ends and instability of mitochondrial DNA. As a result, they produce a distinct profile of metabolites, disproportionally expand their endoplasmic reticulum (ER) membranes and release excess amounts of pro-inflammatory effector cytokines. Characteristically, they are tissue invasive, activate the inflammasome and die a pyroptotic death. Patients with GCA expand pathogenic CD4+ T cells due to aberrant expression of the co-stimulatory receptor NOTCH1 and the failure of the PD-1/PD-L1 immune checkpoint. In addition, GCA patients lose anti-inflammatory Treg cells, promoting tissue-destructive granulomatous vasculitis. In summary, emerging data identify T cell aging as a risk factor for autoimmune disease and directly link TASPs to the breakdown of T cell tolerance and T-cell-induced tissue inflammation.

【 授权许可】

Unknown