title: Immune modulation by MANF promotes tissue repair and regenerative success in the retina.
abstract: Regenerative therapies are limited by unfavorable environments in aging and diseased tissues. A promising strategy to improve success is to balance inflammatory and anti-inflammatory signals and enhance endogenous tissue repair mechanisms. Here, we identified a conserved immune modulatory mechanism that governs the interaction between damaged retinal cells and immune cells to promote tissue repair. In damaged retina of flies and mice, platelet-derived growth factor (PDGF)-like signaling induced mesencephalic astrocyte-derived neurotrophic factor (MANF) in innate immune cells. MANF promoted alternative activation of innate immune cells, enhanced neuroprotection and tissue repair, and improved the success of photoreceptor replacement therapies. Thus, immune modulation is required during tissue repair and regeneration. This approach may improve the efficacy of stem-cell-based regenerative therapies.
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors.forename: Joana
authors.initials: J
authors.lastname: Neves
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Sousa-Victor
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors.forename: Mia
authors.initials: M
authors.lastname: Konjikusic
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors.forename: Rebeccah
authors.initials: R
authors.lastname: Riley
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors.forename: Shereen
authors.initials: S
authors.lastname: Chew
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA. hjasper@buckinstitute.org dlamba@buckinstitute.org.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Jasper
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA. hjasper@buckinstitute.org dlamba@buckinstitute.org.
authors.forename: Deepak A
authors.initials: DA
authors.lastname: Lamba
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004331:Drosophila melanogaster / Q000276:immunology; D004527:Egg Proteins / Q000378:metabolism; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D006434:Hemocytes / Q000276:immunology; D007113:Immunity, Innate; D056747:Immunomodulation; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009414:Nerve Growth Factors / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000276:immunology / Q000494:pharmacology*; D017956:Photoreceptor Cells, Invertebrate / Q000187:drug effects / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D012162:Retinal Degeneration / Q000628:therapy; D015398:Signal Transduction; D014945:Wound Healing / Q000187:drug effects / Q000276:immunology*
chemical_list: D029721:Drosophila Proteins; D004527:Egg Proteins; C539344:MANF protein, Drosophila; C099695:MANF protein, human; C534671:MANF protein, mouse; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D010982:Platelet-Derived Growth Factor; C438367:Pvf1 protein, Drosophila; D011994:Recombinant Proteins; C075278:platelet-derived growth factor A