Post-sepsis immunosuppression depends on NKT cell regulation of mTOR/IFN-γ in NK cells

Kim, Edy Y.; Ner-Gaon, Hadas; Varon, Jack; Cullen, Aidan M.; Guo, Jingyu; Choi, Jiyoung Elizabeth; Barragan-Bradford, Diana; Higuera, Angelica; Pinilla-Vera, Mayra; Short, Samuel A.P.; Arciniegas-Rubio, Antonio J.; Tamura, Tomoyoshi; Leaf, David E.; Baron, Rebecca M.; Shay, Tal; Brenner, Michael B.

doi:10.1172/jci128075

Cited by 70 publications

(69 citation statements)

References 78 publications

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“…Reduced secondary infection to Candida induced by inflammation and sepsis. [170] No effect on immune response RAG2 −/− 3 months…”

Section: Effect Of Rapamycin On the Immune Response To Infectious Agementioning

confidence: 99%

“… Reduced immunosuppression and secondary infection to Candida induced by inflammation and sepsis. [ 170 ] Cd1d −/− F, 10 weeks 0.15 mg, i.p. Reduced secondary infection to Candida induced by inflammation and sepsis.…”

Section: Effect Of Rapamycin On the Immune Response To Infectious Agents In Micementioning

confidence: 99%

“… Reduced secondary infection to Candida induced by inflammation and sepsis. [ 170 ] No effect on immune response RAG2 −/− 3 months 14 ppm No effect on the survival to bacteria, Citrobacter rodentium . [ 44 ] Reduced immune response C57BL/6 M, 6 weeks 1.5 mg/kg, i.p.…”

Section: Effect Of Rapamycin On the Immune Response To Infectious Agents In Micementioning

confidence: 99%

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Effect of rapamycin on aging and age-related diseases—past and future

2020

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In 2009, rapamycin was reported to increase the lifespan of mice when implemented later in life. This observation resulted in a sea-change in how researchers viewed aging. This was the first evidence that a pharmacological agent could have an impact on aging when administered later in life, i.e., an intervention that did not have to be implemented early in life before the negative impact of aging. Over the past decade, there has been an explosion in the number of reports studying the effect of rapamycin on various diseases, physiological functions, and biochemical processes in mice. In this review, we focus on those areas in which there is strong evidence for rapamycin’s effect on aging and age-related diseases in mice, e.g., lifespan, cardiac disease/function, central nervous system, immune system, and cell senescence. We conclude that it is time that pre-clinical studies be focused on taking rapamycin to the clinic, e.g., as a potential treatment for Alzheimer’s disease.

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“…Reduced secondary infection to Candida induced by inflammation and sepsis. [170] No effect on immune response RAG2 −/− 3 months…”

Section: Effect Of Rapamycin On the Immune Response To Infectious Agementioning

confidence: 99%

Section: Effect Of Rapamycin On the Immune Response To Infectious Agents In Micementioning

confidence: 99%

Section: Effect Of Rapamycin On the Immune Response To Infectious Agents In Micementioning

confidence: 99%

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Effect of rapamycin on aging and age-related diseases—past and future

2020

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“…Some clinical trials have demonstrated that adjunctive immunotherapy with interferon γ (IFN-γ) improves the host immune response in sepsis-induced immunosuppression [ 43 ]. However, a recent study demonstrated that IFN-γ produced from invariant natural killer T cells lowered macrophage phagocytosis and promoted post-sepsis immunosuppression [ 44 ]. Collectively, these data suggest that sepsis is a complicated and multistep process that is mediated by temporally precise interactions between different cell types and the integration of multiple signals.…”

Section: Role Of Inflammation In the Pathophysiology Of Sepsismentioning

confidence: 99%

Transglutaminase 2 as a Marker for Inflammation and Therapeutic Target in Sepsis

Qin

Furutani

2021

IJMS

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Sepsis results in lethal organ malfunction due to dysregulated host response to infection, which is a condition with increasing prevalence worldwide. Transglutaminase 2 (TG2) is a crosslinking enzyme that forms a covalent bond between lysine and glutamine. TG2 plays important roles in diverse cellular processes, including extracellular matrix stabilization, cytoskeletal function, cell motility, adhesion, signal transduction, apoptosis, and cell survival. We have shown that the co-culture of Candida albicans and hepatocytes activates and induces the translocation of TG2 into the nucleus. In addition, the expression and activation of TG2 in liver macrophages was dramatically induced in the lipopolysaccharide-injected and cecal ligation puncture-operated mouse models of sepsis. Based on these findings and recently published research, we have reviewed the current understanding of the relationship between TG2 and sepsis. Following the genetic and pharmacological inhibition of TG2, we also assessed the evidence regarding the use of TG2 as a potential marker and therapeutic target in inflammation and sepsis.

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“…In respiratory infection, macrophages promote inflammation resulting in lung injury ( 17 ) and contribute to immune activation in severe acute respiratory disease syndrome ( 18 , 19 ) associated with coronavirus disease of 2019 (COVID-19) ( 20 , 21 ). Macrophage activation states are determined by receptors for an array of environmental signals ( 22 ), with cytokines and microbial molecules as the best known macrophage regulators ( 23 – 25 ). Interferon (IFN)-γ is a key component of classical M1 macrophage activation ( 25 ) and potentiates macrophage responses to subsequent stimulation ( 26 – 28 ).…”

Section: Introductionmentioning

confidence: 99%

SLAMF7 engagement super-activates macrophages in acute and chronic inflammation

Simmons

Nguyen

Gomez-Rivas

et al. 2020

Preprint

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Macrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous macrophage activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with a super-activated macrophage state in rheumatoid arthritis. We implicated IFN-gamma as a key regulator of SLAMF7 expression. Engaging this receptor drove an exuberant wave of inflammatory cytokine expression, and induction of TNF-alpha following SLAMF7 engagement amplified inflammation through an autocrine signaling loop. We observed SLAMF7-induced gene programs not only in macrophages from rheumatoid arthritis patients, but in gut macrophages from active Crohn's disease patients and lung macrophages from severe COVID-19 patients. This suggests a central role for SLAMF7 in macrophage super-activation with broad implications in pathology.

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Post-sepsis immunosuppression depends on NKT cell regulation of mTOR/IFN-γ in NK cells

Cited by 70 publications

References 78 publications

Effect of rapamycin on aging and age-related diseases—past and future

Effect of rapamycin on aging and age-related diseases—past and future

Transglutaminase 2 as a Marker for Inflammation and Therapeutic Target in Sepsis

SLAMF7 engagement super-activates macrophages in acute and chronic inflammation

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