IFN-γIs Protective in Cytokine Release Syndrome-associated Extrapulmonary Acute Lung Injury

• DOI: 10.1165/rcmb.2022-0117oc
• Publication Date: 2022-09-20T13:39:29Z
• Authors: Ying Sun; Buqu Hu; Gail Stanley; Zachary M. Harris; Samir Gautam; Robert Homer; Jonathan L. Koff; Govindarajan Raja...
• Keywords: Superantigen

The mechanisms by which excessive systemic activation of adaptive T lymphocytes, as in cytokine release syndrome (CRS), leads to innate immune cell-mediated acute lung injury (ALI) or respiratory distress syndrome, often the absence any infection, remains unknown. Here, we investigated roles IFN-γ and IL-17A, key T-cell cytokines significantly elevated patients with CRS, immunopathogenesis CRS-induced extrapulmonary ALI. CRS was induced wild-type (WT), IL-17A- knockout (KO) human leukocyte antigen-DR3 transgenic mice 10 μg superantigen, staphylococcal enterotoxin B, given intraperitoneally. Several ALI parameters, including gene expression profiling lungs, were studied 4, 24, 48 hours later. Systemic B resulted robust upregulation several chemokines, S100A8/A9, matrix metalloproteases, other molecules implicated tissue damage, granulocyte well agranulocyte adhesion, diapedesis lungs early 4 hours, accompanied subsequent neutrophil/eosinophil infiltration severe KO mice. These pathways underexpressed IL-17A mice, manifested mildest intermediate WT Neutralization worsened whereas neutralizing did not mitigate suggesting a dominant protective role for that is dispensable. Ruxolitinib, Janus kinase inhibitor, increased severity Thus, our study identified novel its differential modulation IL-17A.