Inflammation rapidly recruits mammalian GMP and MDP from bone marrow into regional lymphatics.

Serrano-Lopez, JuanaHegde, ShailajaKumar, SachinSerrano, JosefinaFang, JingWellendorf, Ashley MRoche, Paul ARangel, YamilethCarrington, Leolene JGeiger, HartmutGrimes, H LeightonLuther, SanjivMaillard, IvanSanchez-Garcia, JoaquinStarczynowski, Daniel TCancelas, Jose A2023-02-092023-02-092021-04-07Serrano-Lopez J, Hegde S, Kumar S, Serrano J, Fang J, Wellendorf AM, et al. Inflammation rapidly recruits mammalian GMP and MDP from bone marrow into regional lymphatics. Elife. 2021 Apr 8;10:e66190http://hdl.handle.net/10668/17543Innate immune cellular effectors are actively consumed during systemic inflammation, but the systemic traffic and the mechanisms that support their replenishment remain unknown. Here, we demonstrate that acute systemic inflammation induces the emergent activation of a previously unrecognized system of rapid migration of granulocyte-macrophage progenitors and committed macrophage-dendritic progenitors, but not other progenitors or stem cells, from bone marrow (BM) to regional lymphatic capillaries. The progenitor traffic to the systemic lymphatic circulation is mediated by Ccl19/Ccr7 and is NF-κB independent, Traf6/IκB-kinase/SNAP23 activation dependent, and is responsible for the secretion of pre-stored Ccl19 by a subpopulation of CD205+/CD172a+ conventional dendritic cells type 2 and upregulation of BM myeloid progenitor Ccr7 signaling. Mature myeloid Traf6 signaling is anti-inflammatory and necessary for lymph node myeloid cell development. This report unveils the existence and the mechanistic basis of a very early direct traffic of myeloid progenitors from BM to lymphatics during inflammation.enCC0 1.0 Universalhttp://creativecommons.org/publicdomain/zero/1.0/Bone marrowCirculationEndotoxemiaHumanImmunologyInflammationLymphaticsMedicineMouseMyeloid progenitorsAdolescentAdultAgedAged, 80 and overAnimalsBone marrowCell lineageCell movementCells, culturedChildChild, preschoolDisease models, animalFemaleGranulocyte-macrophage progenitor cellsHumansInflammationInflammation mediatorsLymphadenopathyLymphatic systemInflammation rapidly recruits mammalian GMP and MDP from bone marrow into regional lymphatics.research article33830019open accessCélulas cultivadasCélulas progenitoras de granulocitos y macrófagosInflamaciónLinaje de la célulaLinfadenopatíaMediadores de inflamaciónModelos animales de enfermedadMovimiento celularSistema linfático10.7554/eLife.661902050-084XPMC8137144https://doi.org/10.7554/elife.66190https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137144/pdf