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This study examined the effects of core and muscle temperature on force steadiness and motor unit discharge rate (MUDR) variability after a hot-water immersion session. Fifteen participants (6 women; 25 ± 6 years) completed neuromuscular assessments before and after either 42 °C (hot) or 36 °C (control) water immersion. Force steadiness was measured during knee extension, while HD-sEMG signals were recorded from vastus lateralis and medialis for MUDR variability analysis. Following water immersion, force steadiness decreased by 0.11% (p < 0.05; d = 0.38) and MUDR variability increased by 1.25% (p < 0.01; d = 0.57) potentially driven by increased muscle temperature. Elevated core temperature did not further affected these changes. [ABSTRACT FROM AUTHOR] more...

The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti–programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti–PD-1. Here, we found that anti–PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of Ruminococcus gnavus in the gut microbiota. Gavage of wild-type mice with R. gnavus enhanced anti–PD-1–mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2. A proinflammatory intestinal environment coincided with expansion, increased circulation, and migration of TNF-producing CD4+ T cells to the tumor bed. Thus, TREM2 remotely controls anti–PD-1 immune checkpoint blockade through modulation of the intestinal immune environment and microbiota, with R. gnavus emerging as a potential probiotic agent for increasing responsiveness to anti-PD-1. Editor's summary: The composition of the gut microbiome affects responses of patients with cancer to immune checkpoint blockade, but the microbiome's involvement in myeloid cell–targeted immunotherapies remains unclear. Di Luccia et al. found that mice lacking the macrophage receptor TREM2 are more responsive to anti–PD-1 tumor immunotherapy because of changes that occur in their gut microbiota. TREM2-deficient mice treated with anti–PD-1 showed expansion of the Gram-positive bacterium Ruminococcus gnavus. Oral treatment of mice with R. gnavus enhanced gut-derived T cell migration to tumors, macrophage proinflammatory gene expression, and tumor responses to anti–PD-1. These findings demonstrate that expansion of specific bacterial species, such as R. gnavus in TREM2-deficient mice, can drive enhanced tumor responses to anti–PD-1 immunotherapy. —Claire Olingy [ABSTRACT FROM AUTHOR] more...

Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). RORγt+ MHCII+ type 3 innate lymphoid cells (ILC3) have also been implicated in the instruction of microbiota-specific Tregs. While RORγt+ APCs have been actively investigated in mice, the identity and function of these cell subsets in humans remain elusive. Herein, we identify a rare subset of RORγt+ cells with dendritic cell (DC) features through integrated single-cell RNA sequencing and single-cell ATAC sequencing. These cells, which we term RORγt+ DC-like cells (R-DC-like), exhibit DC morphology, express the MHC class II machinery, and are distinct from all previously reported DC and ILC3 subsets, but share transcriptional and epigenetic similarities with DC2 and ILC3. We have developed procedures to isolate and expand them in vitro, enabling their functional characterization. R-DC-like cells proliferate in vitro, continue to express RORγt, and differentiate into CD1c+ DC2-like cells. They stimulate the proliferation of allogeneic T cells. The identification of human R-DC-like cells with proliferative potential and plasticity toward CD1c+ DC2-like cells will prompt further investigation into their impact on immune homeostasis, inflammation, and autoimmunity. [ABSTRACT FROM AUTHOR] more...

During prolonged continuous exercise, the relationship between external load (e.g., running speed) and internal load [e.g., heart rate (HR)] shifts. This means, for example, that at a given running speed, the HR will continuously increase, whereas if the goal of the exercise is to maintain a constant HR, the running speed will decrease over time. The time dependence of the internal/external load relationship could lead to different acute responses and chronic adaptations depending on the exercise intensity reference method. This hypothesis was tested in the present study. Forty-three previously inactive individuals were randomized into two groups: one group (SPEED-C) trained at a speed midway between the first and second lactate threshold (v ∆ 50LT), whereas the other group (HR-C) trained at a HR midway between the thresholds (HR ∆ 50LT). Both groups performed 30 min of continuous endurance exercise 3 times per week for 8 weeks. Maximal oxygen consumption (VO2max) and peak treadmill speed (Vpeak) were determined by an incremental treadmill test followed by a verification test before (PRE) and after (POST) the 8 weeks of training. VO2, HR, speed, and rate of perceived exertion (RPE; measured with the Borg CR10) were recorded during the first and last treadmill training sessions performed in the lab. After POST, an additional simulated session was performed with the intensity adjusted to the new training level. Thirty-four participants (9 women and 7 men in SPEED-C; 11 women and 7 men in HR-C) completed the study and were included in the analysis. v ∆ 50LT/HR ∆ 50LT occurred at 74 ± 5% of HRmax, 63 ± 4% of VO2max, and 60 ± 4% of Vpeak in SPEED-C and at 74 ± 5 % of HRmax, 63 ± 5% of VO2max, and 60 ± 6 % of Vpeak in HR-C. SPEED-C showed higher speed (+1.5 km/h, p < .001), VO2 (+6.3 mL/kg/min, p < .001), HR (+23 bpm, p < .001) and RPE (+1.9 points, p = .002) than HR-C during the first training session. These initial differences between groups were reduced after 8 weeks of training (speed: by -0.5 km/h, p = .006; VO2: by -2.6 mL/kg/min, p < .001; HR: by -14 bpm, p < .001; RPE: (-1.7 points, p = .002). However, statistically significant reductions were no longer observed when the intensity was adjusted to the new training level. VO2max (+1.0 mL/kg/min, p = .021) and Vpeak (+0.8 km/h, p < .001) improved more in SPEED-C than in HR-C. Among the secondary physiological characteristics investigated in this study, speed at the second lactate threshold (+1.1 km/h, p < .001) and v ∆ 50LT (+0.5 km/h, p = .008) improved more in SPEED-C than in HR-C, whereas HR at the second lactate threshold improved more in HR-C than in SPEED-C (-7 bpm, p = .008). The exercise intensity reference method (speed vs. HR) affects acute responses and chronic adaptations in previously inactive individuals. However, training conditioning may mitigate these differences if the intensity is not constantly adjusted to the new training level. [ABSTRACT FROM AUTHOR] more...