Dynamic transcriptome analysis unveils key proresolving factors of chronic inflammatory arthritis

Kong, Jin-Sun; Park, Ji-Hwan; Yoo, Sehoon; Kim, Ki-Myo; Bae, Yeung-Jin; Joo, Young Bin; Cho, Chul-Soo; Hwang, Daehee; Kim, Wan‐Uk

doi:10.1172/jci126866

Cited by 13 publications

(19 citation statements)

References 42 publications

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“…M2-like phenotype in wheel runners notwithstanding, the foregoing result of a relatively non-homeostatic macrophage in this group led us to further consider the hypothesis that wheel runners exhibit a broader non-resolved inflammatory state. Not simply representative of one macrophage phenotype, the up-regulated gene set identified by Kong et al (2020) that associates with resolution of a sterile inflammatory event is constituted by multiple myeloid and lymphoid cell subtypes. Following a significant crossover interaction ( P = .002; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Exploratory analyses of the whole tissue transcriptome data suggested that mononuclear phagocytes may be part of an inflammation resolution program that is ultimately down-regulated by physical activity. Voluntary wheel running significantly reduced expression of a gene set ( Kong et al, 2020 ; Data S4 ) that manifests at the resolution of a sterile inflammatory event. In association with the reversal of both monocyte and M2-like macrophage percentages in wheel runners that received clodronate, there was also a reversal of this resolution gene set in wheel runners that received clodronate.…”

Section: Discussionmentioning

confidence: 99%

“…To test for group differences in the prevalence of transcriptomes for monocytic and granulocytic myeloid-derived suppressor cells (M-MDSC and G-MDSC) described by Alshetaiwi et al (2020) , the macrophage lactate timer described by Zhang et al (2019a) , and the inflammation resolution program described by Kong et al, (2020) , we conducted a transcriptome representation analysis (TRA) ( Powell et al, 2013 ). For each of the TRAs, a transcriptome’s composite score was computed for a given subject by calculating the mean expression value, in that subject, of all genes specified in the reference set of the transcriptome in question.…”

Section: Methodsmentioning

confidence: 99%

“…The reference sets for M-MDSCs and G-MDSCs were composed of genes from CD45 + CD11b + Gr1 + phenotypic MDSC cells that best identified functional (i.e., immunosuppressive) MDSCs vs. non-functional MDSCs of both the monocytic and granulocytic lineages, as evidenced by >50% differential expression in the functional cells ( Alshetaiwi et al, 2020 ) ( Data S3 ). Reference set for active resolution of inflammation was composed of genes that were up-regulated by >75% at the resolution of a sterile inflammatory event vs. its peak ( Kong et al, 2020 ) ( Data S4 ). Reference set for the macrophage lactate timer was composed of genes in macrophages that were up-regulated by >100% at 24 h following an M1-promoting pro-inflammatory stimulus in vitro (i.e., LPS) ( Zhang et al, 2019a ) ( Data S5 ).…”

Section: Methodsmentioning

confidence: 99%

“… Peak inflammation from Kong et al (2020) were genes up-regulated by 50% at peak inflammation vs. baseline, before subsequent resolution of inflammation (Supplementary Data 6). Mean ± SEM and individual data points, with n = 5–6 mice per group.…”

Section: Supplemental Informationmentioning

confidence: 99%

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Physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice

Lamkin

Bradshaw

Chang³

et al. 2021

PeerJ

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The risk for breast cancer is significantly reduced in persons who engage in greater amounts of physical activity, and greater physical activity before or after diagnosis associates with reduced disease-specific mortality. Previous mechanistic studies indicate that components of innate immunity can mediate an inhibitory effect of physical activity on several types of tumor. However, in breast cancer specifically, the myeloid compartment of innate immunity is thought to exhibit high propensity for an immunosuppressive role that obstructs anti-tumor immunity. Thus, we tested the notion that greater physical activity alters mononuclear phagocytes in mammary tissue when inhibiting nascent tumor in a murine model of breast cancer. To model greater physical activity, we placed an angled running wheel in each mouse’s home cage for two weeks before tumor engraftment with EO771 mammary cancer cells that express luciferase for bioluminescent detection. Fully immunocompetent mice and mice with compromised adaptive immunity showed significantly less mammary tumor signal when given access to running wheels, although the effect size was smaller in this latter group. To investigate the role of the myeloid compartment, mononuclear phagocytes were ablated by systemic injection of clodronate liposomes at 24 h before tumor engraftment and again at the time of tumor engraftment, and this treatment reversed the inhibition in wheel running mice. However, clodronate also inhibited mammary tumor signal in sedentary mice, in conjunction with an expected decrease in gene and protein expression of the myeloid antigen, F4/80 (Adgre1), in mammary tissue. Whole transcriptome digital cytometry with CIBERSORTx was used to analyze myeloid cell populations in mammary tissue following voluntary wheel running and clodronate treatment, and this approach found significant changes in macrophage and monocyte populations. In exploratory analyses, whole transcriptome composite scores for monocytic myeloid-derived suppressor cell (M-MDSC), macrophage lactate timer, and inflammation resolution gene expression programs were significantly altered. Altogether, the results support the hypothesis that physical activity inhibits nascent mammary tumor growth by enhancing the anti-tumor potential of mononuclear phagocytes in mammary tissue.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Supplemental Informationmentioning

confidence: 99%

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Physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice

Lamkin

Bradshaw

Chang³

et al. 2021

PeerJ

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Arthritic Microenvironment Actuated Nanomotors for Active Rheumatoid Arthritis Therapy

Jiang

Wang

et al. 2022

Advanced Science

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Increasing O 2 demand and excessive ROS production are the main features of arthritic microenvironment in rheumatoid arthritis (RA) joints and further play pivotal roles in inflammation exacerbation. In this work, a system of in situ regulation of arthritic microenvironment based on nanomotor strategy is proposed for active RA therapy. The synthesized MnO 2 -motors enable catalytic regulation of RA microenvironment by consuming the overproduced H 2 O 2 and generating O 2 synergistically. The generated O 2 under H 2 O 2 -rich conditions functions as inflammation detector, propellant for enhanced diffusion, as well as ameliorator for the hypoxic synovial microenvironment. Owing to O 2 generation and inflammation scavenging, the MnO 2 -motors block the re-polarization of pro-inflammatory macrophages, which results in significantly decreased secretion of multiple pro-inflammatory cytokines both in vitro and in vivo. In addition, intra-articular administration of MnO 2 -motors to collagen-induced arthritis rats (CIA rats) effectively alleviates hypoxia, synovial inflammation, bone erosion, and cartilage degradation in joints. Therefore, the proposed arthritic regulation strategy shows great potential to seamlessly integrate basic research of RA with clinical translation.

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Novel insights into macrophage diversity in rheumatoid arthritis synovium

Boutet

Courties

Nerviani

et al. 2021

Autoimmunity Reviews

105

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Dynamic transcriptome analysis unveils key proresolving factors of chronic inflammatory arthritis

Cited by 13 publications

References 42 publications

Physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice

Physical activity modulates mononuclear phagocytes in mammary tissue and inhibits tumor growth in mice

Arthritic Microenvironment Actuated Nanomotors for Active Rheumatoid Arthritis Therapy

Novel insights into macrophage diversity in rheumatoid arthritis synovium

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