Blood:JAK/STAT inhibition enhances the sensitivity of CD8 T cells to desermison-induced apoptosis.

Cytokine Storm Syndrome (CSS) is a severe state of hyper-inflammatory disease characterized by an overactive immune system that causes organ damage and patient death.
HLH is a typical CSS with a five-year survival rate of only 60%, a disease often associated with cell-mediated cytotoxic genetic defects.
first-line treatments for HLH include the glucocorticoid dexamination (DEX) and the chemotherapy drug etoposide.
but many patients are intolerating the treatment or relapse after initial treatment remission.
it is important to note that in HLH, a variety of cytokines increased, activating the JAK/STAT path, and the JAK1/2 inhibitor Rusotini (RUX) has been shown to be effective in mouse HLH models and in patients with incurable diseases.
recently, researchers found that cytokine-induced JAK/STAT signals mediated the resistance of T-cell acute lymphoblastic leukemia (T-ALL) cells to d'isemison, which RUX can effectively reverse.
these findings, Meyer et al. hypothesise that cytokine-mediated JAK/STAT signals may also promote HLH's desemethone resistance, a phenomenon that RUX therapy may be able to overcome.
Through in-body experiments, Meyer et al. demonstrated in HLH mouse models and primary patient samples that HLH's high-cell kinaseemia reduces the apoptosis potential of CD8 T cells, leading to the relative resistance of dexamination.
exposure to RUX, this apoptosis potential is restored, thereby enhancing the sensitivity of CD8 T cells to dexamisson-induced apoptosis in vitro and significantly reducing the performance of tissue immunopathology and HLH disease in the body.
, the results of this study provide a theoretical basis for the combination of DEX and RUX to enhance the lymphotoxic effect of DEX to improve the prognostication of HLH and related CSS patients.
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