title: Active players in resolution of shock/sepsis induced indirect lung injury: immunomodulatory effects of Tregs and PD-1.
abstract: The immunomodulatory effects of PD-1 and CD4(+)CD25(+) Tregs in the resolution of ALI are still poorly understood. Accordingly, 1 million Tregs were isolated from spleens of WT C57BL/6 or PD-1(-/-) mice (magnetical bead purification and subsequent labeling with/without Vybrant dye) and then AT into mice subjected to Hem shock during their resuscitation period, which were subsequently subjected to CLP/septic challenge (24 h post-Hem) to induce iALI. Initially, we demonstrated that Vybrant-labeled AT Tregs appear in the lungs of iALI mice. Subsequently, we found that AT of WT Tregs induced a significant repression of the indices of lung injury: a reduction of neutrophil influx to the lung tissue and a decrease of lung apoptosis compared with vehicle-treated iALI mice. In addition, these mice had substantially higher concentrations of BALF and lung-tissue IL-10 but significantly decreased levels of lung KC. However, these beneficial effects of the AT of Tregs were lost with the administration of PD-1(-/-) mouse Tregs to the recipient WT mice. ALI was exacerbated in these recipient mice receiving AT PD-1(-/-) Tregs to the same extent as iALI mice that did not receive Tregs. These data imply that Tregs can act directly to modify the innate immune response induced by experimental iALI, and this is mediated, in part, by PD-1. Hence, the manipulation of Tregs may represent a plausible target for treating iALI.
authors.affiliation: Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai, China; and.
authors.forename: Lunxian
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai, China; and.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Surgery, Division of Surgical Research, Alpert School of Medicine at Brown University/Rhode Island Hospital, Providence, Rhode Island, USA.
authors.forename: Chun-Shiang
authors.initials: CS
authors.lastname: Chung
authors.affiliation: Department of Surgery, Division of Surgical Research, Alpert School of Medicine at Brown University/Rhode Island Hospital, Providence, Rhode Island, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Lomas-Neira
authors.affiliation: Department of Surgery, Division of Surgical Research, Alpert School of Medicine at Brown University/Rhode Island Hospital, Providence, Rhode Island, USA.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Surgery, Division of Surgical Research, Alpert School of Medicine at Brown University/Rhode Island Hospital, Providence, Rhode Island, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Surgery, Division of Surgical Research, Alpert School of Medicine at Brown University/Rhode Island Hospital, Providence, Rhode Island, USA aayala@lifespan.org.
authors.forename: Alfred
authors.initials: A
authors.lastname: Ayala
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D019264:Adoptive Transfer; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D060908:CTLA-4 Antigen / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D056747:Immunomodulation; D016130:Immunophenotyping; D018836:Inflammation Mediators; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D012772:Shock, Septic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: D060908:CTLA-4 Antigen; D016207:Cytokines; D018836:Inflammation Mediators; D061026:Programmed Cell Death 1 Receptor; D009195:Peroxidase; D053148:Caspase 3
keywords: ARDS; adoptive transfer; apoptosis; chemokine; neutrophil influx
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