ArticleInvestigative ophthalmology & visual science2011
Macrophage IL-12p70 signaling prevents HSV-1-induced CNS autoimmunity triggered by autoaggressive CD4+ Tregs.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Epigenetic profiling reveals M1 macrophages as the primary drivers of trained immunity in HSV-1 latently infected mice.PLoS pathogens · 2026Article
- HSV-1 Infection Differentially Modulates NPY and VIP Neuropeptide Expression in the Mouse Brain and in Human Neuronal Cells.International journal of molecular sciences · 2026Article
- Divergent roles of macrophage subsets, FoxP3, and IL-17A in HSV-1-induced CNS pathology.PLoS pathogens · 2025Article
- IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination.Frontiers in immunology · 2023Article
- Blocking Autophagy in M1 Macrophages Enhances Virus Replication and Eye Disease in Ocularly Infected Transgenic Mice.Journal of virology · 2022Article
- Type 2 Innate Lymphoid Cells Induce CNS Demyelination in an HSV-IL-2 Mouse Model of Multiple Sclerosis.iScience · 2020Article
- Roles of M1 and M2 Macrophages in Herpes Simplex Virus 1 Infectivity.Journal of virology · 2017Article
- Suppression of IL-12p70 formation by IL-2 or following macrophage depletion causes T-cell autoreactivity leading to CNS demyelination in HSV-1-infected mice.PLoS pathogens · 2017Article
- Prophylactic and therapeutic modulation of innate and adaptive immunity against mucosal infection of herpes simplex virus.Immune network · 2014Review
- A comparative study of experimental mouse models of central nervous system demyelination.Gene therapy · 2014Article
- The expression of IL-2 and IL-4 in CD4(+) T cells from mouse lymph nodes and spleen during HSV-1-induced facial palsy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2014Article
- Role of interleukin-2 and herpes simplex virus 1 in central nervous system demyelination in mice.Journal of virology · 2013Article
- The effect of mouse strain on herpes simplex virus type 1 (HSV-1) infection of the central nervous system (CNS).Herpesviridae · 2012Article
- Treg cell resistance to apoptosis in DNA vaccination for experimental autoimmune encephalomyelitis treatment.PloS one · 2012Article
- Immune response of T cells during herpes simplex virus type 1 (HSV-1) infection.Journal of Zhejiang University. Science. BReview
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
purposeCD4(+)CD25(+)FoxP3(+) naturally occurring regulatory T cells (Tregs) maintain self-tolerance and function to suppress overly exuberant immune responses. However, it is unclear whether innate immune cells modulate Treg function. Here the authors examined the role of innate immunity in lymphomyeloid homeostasis.
methodsThe involvement of B cells, dendritic cells (DCs), macrophages, natural killer (NK) cells, and T cells in central nervous system (CNS) demyelination in different strains of mice infected ocularly with herpes simplex virus type 1 (HSV-1) was investigated.
resultsThe authors found that depletion of macrophages, but not DCs, B cells, NK cells, CD4(+) T cells, or CD8(+) T cells, induced CNS demyelination irrespective of virus or mouse strain. As with macrophage depletion, mice deficient in interleukin (IL)-12p35 or IL-12p40 showed CNS demyelination after HSV-1 infection, whereas demyelination was undetectable in HSV-1-infected, IL-23p19-deficient, or Epstein-Barr virus-induced gene 3-deficient mice. Demyelination could be rescued in macrophage-depleted mice after the injection of IL-12p70 DNA and in IL-12p35(-/-) or IL-12p40(-/-) mice after injection with IL-12p35 or IL-12p40 DNA or with recombinant viruses expressing IL-12p35 or IL-12p40. Using FoxP3-, CD4-, CD8-, or CD25-depletion and gene-deficient mouse approaches, the authors demonstrated that HSV-1-induced demyelination was blocked in the absence of CD4, CD25, or FoxP3 in macrophage-depleted mice. Flow cytometry showed an elevation of CD4(+)CD25(+)FoxP3(+) T cells in the spleens of infected macrophage-depleted mice, and adoptive transfer of CD4(+)CD25(+) T cells to infected macrophage-depleted severe combined immunodeficient mice induced CNS demyelination.
conclusionsThe authors demonstrated that macrophage IL-12p70 signaling plays an important role in maintaining immune homeostasis in the CNS by preventing the development of autoaggressive CD4(+) Tregs.
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