A new nucleic acid–based agent inhibits cytotoxic T lymphocyte–mediated immune disorders

Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions

“…We determined whether the enrolled participants had SJS-TEN using the Registry of Severe Cutaneous Adverse ReacOver the past 2 decades, studies have shown that the pathomechanism of SJS-TEN is associated with the effector cytotoxic T lymphocytes (CTLs) that recognize culprit drugs presented by HLA class I molecules on keratinocytes (6)(7)(8)(9) (8,10,11). We have previously identified secretory granulysin as a key mediator that leads to disseminated keratinocyte apoptosis and detachment of the epidermis and mucous membranes in SJS-TEN (12,13). Granulysin is known to be generated by CTLs, NK cells, and NKT cells and released into the extracellular environment along with other cytotoxic mediators (such as soluble FasL, granzyme B, and perforin) (12,(14)(15)(16).…”

Manipulating the in vivo immune response by targeted gene knockdown

“…Aptamer-siRNAs have been developed to knockdown gene expression in all CD4 cells [7,8,61] or CD8 [62] T cells. My group designed CD4-AsiCs to knockdown gene expression in all CD4+ cells susceptible to HIV infection and showed that knockdown of CCR5 , the HIV coreceptor used in sexual transmission, or knockdown of HIV genes by vaginally applied AsiCs prevented genital transmission of HIV to humanized mice [7,8].…”

“…It will be interesting to examine what happens when the master transcription factors for T cell differentiation are knocked down in vivo. For directed gene knockdown in CD8 T cells, a DNA aptamer for CD8 was annealed via a “sticky bridge” adapter to an siRNA and shown to induce CD8 cell-specific gene knockdown in vitro [62]. So far no in vivo experiments involving directed gene knockdown via the CD8+ receptor have been reported.…”

MicroRNA and gene signature of severe cutaneous drug hypersensitivity reactions reveal the role of miR-483- 5p/miR-28-5p in inflammation by targeting Granulysin gene

“…T-cell lymphocyte association with SJS and TEN was recently observed to be linked with skin reactions, in addition to the recently reported Granulysin and natural killer cells inhibitory receptors [9]. Currently, Granulysin acts as the substantial player and responsible for the dispersed keratinocyte death [10] and it has a role in cytotoxic T lymphocyte conditions [11].…”