American journal of respiratory and critical care medicine
Authors: Thakur N, Lovinsky-Desir S, Bime C, Wisnivesky JP, Celedón JC
Nature communications
Authors: Terranova-Barberio M, Pawlowska N, Dhawan M, Moasser M, Chien AJ, Melisko ME, Rugo H, Rahimi R, Deal T, Daud A, Rosenblum MD, Thomas S, Munster PN
The New England journal of medicine
Authors: STARRT-AKI Investigators, Canadian Critical Care Trials Group, Australian and New Zealand Intensive Care Society Clinical Trials Group, United Kingdom Critical Care Research Group, Canadian Nephrology Trials Network, Irish Critical Care Trials Group, Bagshaw SM, Wald R, Adhikari NKJ, Bellomo R, da Costa BR, Dreyfuss D, Du B, Gallagher MP, Gaudry S, Hoste EA, Lamontagne F, Joannidis M, Landoni G, Liu KD, McAuley DF, McGuinness SP, Neyra JA, Nichol AD, Ostermann M, Palevsky PM, Pettilä V, Quenot JP, Qiu H, Rochwerg B, Schneider AG, Smith OM, Thomé F, Thorpe KE, Vaara S, Weir M, Wang AY, Young P, Zarbock A
Scientific Reports
Authors: Almodovar S, Wade BE, Porter KM, Smith JM, Lopez-Astacio RA, Bijli K, Kang BY, Cribbs SK, Guidot DM, Molehin D, McNair BK, Pumarejo-Gomez L, Perez Hernandez J, Salazar EA, Martinez EG, Huang L, Kessing CF, Suarez-Martinez EB, Pruitt K, Hsue PY, Tyor WR, Flores SC, Sutliff RL
JAMA oncology
Authors: Enzinger AC, Uno H, McCleary N, Frank E, Sanoff H, Van Loon K, Matin K, Bullock A, Cronin C, Cibotti H, Bagley J, Schrag D
Nature communications
Authors: Strunz M, Simon LM, Ansari M, Kathiriya JJ, Angelidis I, Mayr CH, Tsidiridis G, Lange M, Mattner LF, Yee M, Ogar P, Sengupta A, Kukhtevich I, Schneider R, Zhao Z, Voss C, Stoeger T, Neumann JHL, Hilgendorff A, Behr J, O'Reilly M, Lehmann M, Burgstaller G, Königshoff M, Chapman HA, Theis FJ, Schiller HB
Journal of analytical toxicology
Authors: Melamed J, Gerona R, Blanc PD, Takamoto P, Conner S, Goodnough R
JAMA oncology
Authors: Puzanov I, Ribas A, Robert C, Schachter J, Nyakas M, Daud A, Arance A, Carlino MS, O'Day SJ, Long GV, Margolin KA, Dummer R, Schadendorf D, Lutzky J, Ascierto PA, Tarhini A, Lin J, Mogg R, Homet Moreno B, Ibrahim N, Hamid O
Psycho-oncology
Authors: Jhaveri K, Cohen JA, Barulich M, Levin AO, Goyal N, Loveday T, Chesney MA, Shumay DM
Volume 12 of Issue 552 | Science translational medicine
Authors: Bader CS, Barreras H, Lightbourn CO, Copsel SN, Wolf D, Meng J, Ahn J, Komanduri KV, Blazar BR, Jin L, Barber GN, Roy S, Levy RB
The stimulator of interferon genes (STING) pathway has been proposed as a key regulator of gastrointestinal homeostasis and inflammatory responses. Although STING reportedly protects against gut barrier damage and graft-versus-host disease (GVHD) after major histocompatibility complex (MHC)-mismatched allogeneic hematopoietic stem cell transplantation (aHSCT), its effect in clinically relevant MHC-matched aHSCT is unknown. Studies here demonstrate that STING signaling in nonhematopoietic cells promoted MHC-matched aHSCT-induced GVHD and that STING agonists increased type I interferon and MHC I expression in nonhematopoietic mouse intestinal organoid cultures. Moreover, mice expressing a human STING allele containing three single-nucleotide polymorphisms associated with decreased STING activity also developed reduced MHC-matched GVHD, demonstrating STING's potential clinical importance. STING recipients experienced reduced GVHD with transplant of purified donor CD8 T cells in both MHC-matched and MHC-mismatched models, reconciling the seemingly disparate results. Further examination revealed that STING deficiency reduced the activation of donor CD8 T cells early after transplant and promoted recipient MHC class II antigen-presenting cell (APC) survival. Therefore, APC persistence in STING pathway absence may account for the increased GVHD mediated by CD4 T cells in completely mismatched recipients. In total, our findings have important implications for regulating clinical GVHD by targeting STING early after aHSCT and demonstrate that an innate immune pathway has opposing effects on the outcome of aHSCT, depending on the donor/recipient MHC disparity.
View on PubMed
