TY - JOUR
T1 - NK Cell-Derived IL-10 Supports Host Survival during Sepsis
AU - Jensen, Isaac J.
AU - McGonagill, Patrick W.
AU - Butler, Noah S.
AU - Harty, John T.
AU - Griffith, Thomas S.
AU - Badovinac, Vladimir P.
N1 - Publisher Copyright:
© 2021 American Association of Immunologists. All rights reserved.
PY - 2021/3/15
Y1 - 2021/3/15
N2 - The dysregulated sepsis-induced cytokine storm evoked during systemic infection consists of biphasic and interconnected pro- A nd anti-inflammatory responses. The contrasting inflammatory cytokine responses determine the severity of the septic event, lymphopenia, host survival, and the ensuing long-lasting immunoparalysis state. NK cells, because of their capacity to elaborate pro-(i.e., IFN-g) and anti-inflammatory (i.e., IL-10) responses, exist at the inflection of sepsis-induced inflammatory responses. Thus, NK cell activity could be beneficial or detrimental during sepsis. In this study, we demonstrate that murine NK cells promote host survival during sepsis by limiting the scope and duration of the cytokine storm. Specifically, NK cell-derived IL-10, produced in response to IL-15, is relevant to clinical manifestations in septic patients and critical for survival during sepsis. This role of NK cells demonstrates that regulatory mechanisms of classical inflammatory cells are beneficial and critical for controlling systemic inflammation, a notion relevant for therapeutic interventions during dysregulated infection-induced inflammatory responses. The Journal of Immunology, 2021, 206: 1171-1180.
AB - The dysregulated sepsis-induced cytokine storm evoked during systemic infection consists of biphasic and interconnected pro- A nd anti-inflammatory responses. The contrasting inflammatory cytokine responses determine the severity of the septic event, lymphopenia, host survival, and the ensuing long-lasting immunoparalysis state. NK cells, because of their capacity to elaborate pro-(i.e., IFN-g) and anti-inflammatory (i.e., IL-10) responses, exist at the inflection of sepsis-induced inflammatory responses. Thus, NK cell activity could be beneficial or detrimental during sepsis. In this study, we demonstrate that murine NK cells promote host survival during sepsis by limiting the scope and duration of the cytokine storm. Specifically, NK cell-derived IL-10, produced in response to IL-15, is relevant to clinical manifestations in septic patients and critical for survival during sepsis. This role of NK cells demonstrates that regulatory mechanisms of classical inflammatory cells are beneficial and critical for controlling systemic inflammation, a notion relevant for therapeutic interventions during dysregulated infection-induced inflammatory responses. The Journal of Immunology, 2021, 206: 1171-1180.
UR - http://www.scopus.com/inward/record.url?scp=85102724385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102724385&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.2001131
DO - 10.4049/jimmunol.2001131
M3 - Article
C2 - 33514512
AN - SCOPUS:85102724385
SN - 0022-1767
VL - 206
SP - 1171
EP - 1180
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -