Publications by authors named "Matt Schaller"

2 Publications

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Epigenetic stabilization of DC and DC precursor classical activation by TNFα contributes to protective T cell polarization.

Sci Adv 2019 12 4;5(12):eaaw9051. Epub 2019 Dec 4.

Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109, USA.

Epigenetic modifications play critical roles in inducing long-lasting immunological memory in innate immune cells, termed trained immunity. Whether similar epigenetic mechanisms regulate dendtritic cell (DC) function to orchestrate development of adaptive immunity remains unknown. We report that DCs matured with IFNγ and TNFα or matured in the lungs during invasive fungal infection with endogenous TNFα acquired a stable TNFα-dependent DC1 program, rendering them resistant to both antigen- and cytokine-induced alternative activation. TNFα-programmed DC1 had increased association of H3K4me3 with DC1 gene promoter regions. Furthermore, MLL1 inhibition blocked TNFα-mediated DC1 phenotype stabilization. During IFI, TNFα-programmed DC1s were required for the development of sustained T1/T17 protective immunity, and bone marrow pre-DCs exhibited TNFα-dependent preprogramming, supporting continuous generation of programmed DC1 throughout the infection. TNFα signaling, associated with epigenetic activation of DC1 genes particularly via H3K4me3, critically contributes to generation and sustenance of type 1/17 adaptive immunity and the immune protection against persistent infection.
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http://dx.doi.org/10.1126/sciadv.aaw9051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892624PMC
December 2019

Murine macrophage chemokine receptor CCR2 plays a crucial role in macrophage recruitment and regulated inflammation in wound healing.

Eur J Immunol 2018 09 26;48(9):1445-1455. Epub 2018 Jun 26.

Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

Macrophages play a critical role in the establishment of a regulated inflammatory response following tissue injury. Following injury, CCR2 monocytes are recruited from peripheral blood to wound tissue, and direct the initiation and resolution of inflammation that is essential for tissue repair. In pathologic states where chronic inflammation prevents healing, macrophages fail to transition to a reparative phenotype. Using a murine model of cutaneous wound healing, we found that CCR2-deficient mice (CCR2 ) demonstrate significantly impaired wound healing at all time points postinjury. Flow cytometry analysis of wounds from CCR2 and WT mice revealed a significant decrease in inflammatory, Ly6C recruited monocyte/macrophages in CCR2 wounds. We further show that wound macrophage inflammatory cytokine production is decreased in CCR2 wounds. Adoptive transfer of mT/mG monocyte/macrophages into CCR2 and CCR2 mice demonstrated that labeled cells on days 2 and 4 traveled to wounds in both CCR2 and CCR2 mice. Further, adoptive transfer of monocyte/macrophages from WT mice restored normal healing, likely through a restored inflammatory response in the CCR2-deficient mice. Taken together, these data suggest that CCR2 plays a critical role in the recruitment and inflammatory response following injury, and that wound repair may be therapeutically manipulated through modulation of CCR2.
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http://dx.doi.org/10.1002/eji.201747400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371802PMC
September 2018