PARP-1 is critical for recruitment of dendritic cells to the lung in a mouse model of asthma but dispensable for their differentiation and function

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  • dc.contributor.author Echeverri Tirado, Laura C.
  • dc.contributor.author Ghonim, Mohamed A.
  • dc.contributor.author Wang, Jeffrey
  • dc.contributor.author Al-Khami, Amir A.
  • dc.contributor.author Wyczechowska, Dorota
  • dc.contributor.author Luu, Hanh H.
  • dc.contributor.author Hogyoung, Kim
  • dc.contributor.author Sanchez-Pino, Maria Dulfary
  • dc.contributor.author Yélamos López, José
  • dc.contributor.author Yassin, Lina M.
  • dc.contributor.author Boulares, A. Hamid
  • dc.date.accessioned 2020-03-02T08:32:30Z
  • dc.date.available 2020-03-02T08:32:30Z
  • dc.date.issued 2019
  • dc.description.abstract Dendritic cells (DCs) are critical in asthma and many other immune diseases. We previously demonstrated a role for PARP-1 in asthma. Evidence on PARP-1 playing a role in Th2-associated DC function is not clear. In this study, we examined whether PARP-1 is critical for DC differentiation and function using bone marrow progenitors and their migration to the lung in an ovalbumin-based mouse model of asthma. Results show that changes in PARP-1 levels during GM-CSF-induced DC differentiation from bone marrow progenitors were cyclic and appear to be part of an array of changes that included STAT3/STAT5/STAT6/GRAIL/RAD51. Interestingly, PARP-1 gene deletion affected primarily STAT6 and γH2AX. PARP-1 inhibition significantly reduced the migration of DCs to the lungs of ovalbumin-challenged mice, which was associated with a concomitant reduction in lung levels of the adhesion molecule VCAM-1. The requirement of PARP-1 for VCAM-1 expression was confirmed using endothelial and lung smooth muscle cells. PARP-1 expression and activity were also required for VCAM-1 in differentiated DCs. An assessment of CD11b+/CD11c+/MHCIIhigh DCs in spleens and lymph nodes of OVA-sensitized mice revealed that PARP-1 inhibition genetically or by olaparib exerted little to no effect on DC differentiation, percentage of CD80+/CD86+/CD40+-expressing cells, or their capacity to promote proliferation of ovalbumin-primed (OTII) CD4+ T cells. These findings were corroborated using GM-CSF-induced differentiation of DCs from the bone marrow. Surprisingly, the PARP-1-/- DCs exhibited a higher intrinsic capacity to induce OTII CD4+ T cell proliferation in the absence of ovalbumin. Overall, our results show that PARP-1 plays little to no role in DC differentiation and function and that the protective effect of PARP-1 inhibition against asthma is associated with a prevention of DC migration to the lung through a reduction in VCAM-1 expression. Given the current use of PARP inhibitors (e.g., olaparib) in the clinic, the present results may be of interest for the relevant therapies.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Echeverri Tirado LC, Ghonim MA, Wang J, Al-Khami AA, Wyczechowska D, Luu HH. Et al. PARP-1 is critical for recruitment of dendritic cells to the lung in a mouse model of asthma but dispensable for their differentiation and function. Mediators Inflamm. 2019 Apr 24; 2019:1656484. DOI: 10.1155/2019/1656484
  • dc.identifier.doi http://dx.doi.org/10.1155/2019/1656484
  • dc.identifier.issn 0962-9351
  • dc.identifier.uri http://hdl.handle.net/10230/43757
  • dc.language.iso eng
  • dc.publisher Hindawi
  • dc.rights Copyright © 2019 Laura C. Echeverri Tirado et al. This is an open access article distributed under the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/ which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.other PARP-1
  • dc.subject.other Asma
  • dc.subject.other Pulmons -- Malalties
  • dc.title PARP-1 is critical for recruitment of dendritic cells to the lung in a mouse model of asthma but dispensable for their differentiation and function
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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