Inflammatory microenvironments play a key role in skeletal muscle regeneration. The infiltration of CD8 T cells into injured muscle has been reported. However, the role of CD8 T cells during skeletal muscle regeneration remains unclear. In this study, we used cardiotoxin-induced mouse skeletal muscle injury/regeneration model to investigate the role of CD8 T cells. Muscle regeneration was impaired and matrix deposit was increased in CD8α-deficient mice compared with wild-type (WT) mice whose CD8 T cells were infiltrated into damaged muscle after cardiotoxin injection. Adoptive transfer of CD8 T cells to CD8α-deficient mice improved muscle regeneration and inhibited matrix remodeling. Compared with WT mice, CD8α deficiency limited the recruitment of Gr1high macrophages (MPs) into muscle, resulting in the reduction of satellite cell number. The expression of MCP-1 (MCP-1/CCL2), which regulates the migration of Gr1high MPs, was reduced in CD8α-deficient mice compared with WT mice. Coculture CD8 T cells with MPs promoted MCP-1 secretion. The i.m. injection of MCP-1 markedly promoted the recruitment of Gr1high MPs and improved muscle regeneration in CD8α-deficient mice. We conclude that CD8 T cells are involved in skeletal muscle regeneration by regulating the secretion of MCP-1 to recruit Gr1high MPs, which facilitate myoblast proliferation.

IL-17A-producing T lymphocytes play a crucial role in inflammatory kidney diseases, but their role in renal fibrosis remains to be explored. Here, we demonstrated that up-regulation of IL-17A was associated with the development of obstructive kidney injury. The primary source of IL-17A production in obstructed kidneys was infiltrating γδ T lymphocytes and CD4(+) T cells. IL-17A-deficient mice were protected from myofibroblast activation and extracellular matrix deposition, leading to reduced kidney fibrosis in response to obstructive injury. Mechanistically, IL-17A deficiency suppressed the expression of the chemokine RANTES in infiltrated CD3(+) T cells and peritubular inflammation following renal obstruction. Administration of RANTES-neutralizing antibody significantly reduced the accumulation of T cells and macrophages, and of collagen deposition in obstructed kidneys. Taken together, our results indicate that IL-17A contributes significantly to the pathogenesis of renal fibrosis by regulating RANTES-mediated inflammatory cell infiltration.

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Chemokines modulate inflammatory responses that are prerequisites for kidney injury. The specific role of monocyte-associated CX3CR1 and its cognate ligand CX3CL1 in unilateral ureteral obstruction (UUO)–induced kidney injury remains unclear. In this study, we found that UUO caused a CCR2-dependent increase in numbers of Ly6Chi monocytes both in the blood and kidneys and of Ly6C−CX3CR1+ macrophages in the obstructed kidneys of mice. Using CX3CR1gfp/+ knockin mice, we observed a rapid conversion of infiltrating proinflammatory Ly6C+CX3CR11o monocytes/macrophages to anti-inflammatory Ly6C−CX3CR1hi macrophages. CX3CR1 deficiency affected neither monocyte trafficking nor macrophage differentiation in vivo upon renal obstruction, but CX3CR1 expression in monocytes and macrophages was required for increases in fibrosis in the obstructed kidneys. Mechanistically, CX3CL1–CX3CR1 interaction increases Ly6C−CX3CR1hi macrophage survival within the obstructed kidneys. Therefore, CX3CL1 and CX3CR1 may represent attractive therapeutic targets in obstructive nephropathy.

Background: Optical coherence tomography (OCT) is a promising new method of quantifying axon thickness in the retinal nerve fiber layer (RNFL) that has been used predominantly by ophthalmologists to monitor glaucoma. Optical coherence tomography is being considered as a potential outcome measure in multiple sclerosis (MS) clinical trials, but no data exist on the reproducibility of this technique in MS centers. Objective: To determine the reproducibility of OCT measurement of mean RNFL thickness in the undilated eyes of healthy control subjects and patients with MS. Design: Prospective analysis of 4 healthy controls to determine interrater, intrarater, and longitudinal reproducibility. Cross-sectional analysis of 3 cohorts of patients with MS (n=396) and healthy controls (n = 153). Setting: Multiple sclerosis clinics at 3 academic medical centers. Patients or Other Participants: Healthy controls and patients with MS. Main Outcome Measure: Thickness of RNFL. Results: We found excellent agreement with respect to interrater (intraclass correlation [ICC], 0.89), intrarater (ICC, 0.98), and intervisit (ICC, 0.91) results. Mean RNFL thickness did not vary significantly among research centers for patients with MS (93, 92, and 90 µm) or among healthy controls (103, 105, and 104 µm) by site. Conclusions: We demonstrate that mean RNFL thickness can be reproducibly measured by trained technicians in an MS center using the OCT-3 model. The RNFL measures from cohorts of age-matched controls and patients with MS from 3 different research centers were remarkably similar.

In spinal fusion surgery, total blood loss (TBL) is composed of visible blood loss from the surgical field and wound drainage, and hidden blood loss (HBL). Until now, no published studies exist reporting the effect of topical use of tranexamic acid (tTXA) on HBL in patients undergoing posterior lumbar spinal fusion surgery. This study aimed to explore the effect of tTXA on HBL during primary posterior lumbar spinal fusion surgery. Between September 2014 and September 2016, 100 adult patients (age > 18 years) with lumbar disc herniation or lumbar spinal stenosis undergoing primary posterior lumbar instrumented spinal fusions at 1 institution were divided into tTXA and control groups. The primary outcome was HBL. Secondary outcomes include TBL, intraoperative blood loss (IBL), postoperative blood loss (PBL), hemoglobin (HGB) levels on preoperative (Pre-op) and postoperatively (days 1–3, POD1, POD2, POD3, respectively), and amount of allogeneic blood transfusion. Complications occurring perioperatively until hospitalization discharge were also collected. In the tTXA group (n = 50 patients), wound surface was soaked with TXA (1 g in 100 mL saline solution) for 5 minutes before wound closure. For the control group (n = 50 patients), wound surface was soaked with the same volume of normal saline. There were no significant differences in demographics, surgical traits between the 2 groups. There were no significant differences in IBL or perioperative blood transfusion requirements between the 2 groups. However, in the tTXA group, TBL, PBL, and HBL were significantly lower than those in the control group (550 ± 268 vs 833 ± 298 mL, 53.5 ± 43.9 vs 136.7 ± 87.9 mL, 356.7 ± 254.8 vs 501.1 ± 216.9 mL, P < .001, respectively). HGB levels were significantly higher in the tTXA group (P < .001) on POD1 and had a slower decline on POD2 and POD3 than the control group. No complications associated with TXA were observed. From these data, we conclude that tTXA can effectively reduce HBL, without significant complications in adult patients undergoing posterior lumbar spinal fusion surgery.

Background: AMPK senses energetic changes and regulates glucose metabolism. Results: AMPK ␣2 deficiency aggravated the glucose deprivation and necrosis of the hepatocytes via increased ROS production and decreased mitophagy. Conclusion: AMPK ␣2 is essential for attenuation of liver injury during tumor metastasis. Significance: This is the first time to reveal the mechanism by which glucose/energy competition induced tissue damage in tumor.

TGFβ1/Smad, Wnt/β-catenin and snail1 are preferentially activated in renal tubular epithelia after injury, leading to epithelial-mesenchymal transition (EMT). The stress response is coupled to EMT and kidney injury; however, the underlying mechanism of the stress response in EMT remains elusive. AMP-activated protein kinase (AMPK) signalling is responsive to stress and regulates cell energy balance and differentiation. We found that knockdown of AMPKα, especially AMPKα2, enhanced EMT by up-regulating β-catenin and Smad3 in vitro. AMPKα2 deficiency enhanced EMT and fibrosis in a murine unilateral ureteral obstruction (UUO) model. AMPKα2 deficiency also increased the expression of chemokines KC and MCP-1, along with enhanced infiltration of inflammatory cells into the kidney after UUO. CK2β interacted physically with AMPKα and enhanced AMPKα Thr172 phosphorylation and its catalytic activity. Thus, activated AMPKα signalling suppresses EMT and secretion of chemokines in renal tubular epithelia through interaction with CK2β to attenuate renal injury.