Paper Reading
01
Regulatory T CellsPromoteMacrophageEfferocytosis duringInflammationResolution
Jonathan D. Proto, Amanda C. Doran, et al.
Immunity
Treg cells, by suppressing the inflammatoryactivity of both innate and adaptive immune cells and by secreting proteins involved in tissue repair, are poised to play an important role in the inflammationresolution response. In this paper the researchers used multiple methds to try to find the processes linked through Treg-cell-mediated enhancement of efferocytosis in the inflammation resolution response, and finally showed that Treg cells enhanced the ability of macrophages to engulf apoptotic cells (efferocytosis)and thereby promoted resolution of inflammation. In Zymosan-Induced Peritonitismice model, they found depletion of Treg cells reduced the efferocytic capacity of peritoneal macrophages, which suggested that Treg cells played an important role in the clearance of apoptotic cells during the resolution phase of zymosan-induced peritonitis. In order to determine whether Treg cells promoted macrophage efferocytosis during ALI, they subjected Foxp3-hDTR mice to LPS-induced acute lung injury (ALI). They also found Treg Cells depletion during the resolution phase after ALI reduced efferocytosis by airspace Macrophages, and Treg cell transfer to mice with atherosclerosis improves lesional efferocytosis. Mechanistic studies in this paper finally revealed the following sequence: Treg cells secrete IL-13, which stimulates IL-10production in macrophages. Autocrine-paracrine signaling by IL-10 induced Vav1 in macrophages, which activates Rac1 and apoptotic cell engulfment. In summary, Treg cells promote macrophage efferocytosis during inflammation resolution via a transcellular signaling pathway that enhances apoptotic cell internalization.
This paper showed us a plausible link among defects in Treg cells, IL-10, IL-13, and efferocytosis in plaque progression and thereby raised the possibility that therapeutically boosting this axis might prevent atherothrombotic disease in subjects at high risk.
/10.1016/j.immuni..07.015
02
Nrf2 suppressesmacrophageinflammatoryresponse by blockingproinflammatory cytokine transcription
Eri H. Kobayashi,Takafumi Suzuki, et al..
Nature Communications
Nrf2 (NF-E2-related factor-2) transcription factor regulates oxidative/xenobiotic stress response and also represses inflammation. In this paper, to find the molecular basis of the Nrf2 functions of anti-inflammation, two important points have been clarified. First, the researchers discovered that Nrf2 inhibits the LPS-induced expression of proinflammatory cytokine genes, including IL6 and IL1b, through the ROS-independent transcriptional inhibition. Second, they found Nrf2-mediated inhibition of the inflammatory cytokine gene expression in M1 macrophages is ARE-independent. And in the end, they found Nrf2 inhibited Pol II recruitment to the TSSs of the IL6 and IL1b genes without affecting the NF-kB recruitment required for the expression of IL6 and IL1b genes. This study identifies Nrf2 as the upstream regulator of cytokine production and establishes a molecular basis for an Nrf2-mediated anti-inflammation approach.
DOI: 10.1038/ncomms11624
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