Smad2/4 Signaling Pathway Is Critical for Epidermal Langerhans Cell Repopulation Under Inflammatory Condition but Not Required for Their Homeostasis at Steady State

Bibliographic Details
Title: Smad2/4 Signaling Pathway Is Critical for Epidermal Langerhans Cell Repopulation Under Inflammatory Condition but Not Required for Their Homeostasis at Steady State
Authors: Linting Huang, Gui-Hua Li, Qian Yu, Yingping Xu, Steven Cvetkovski, Xuan Wang, Nirmal Parajuli, Imo Udo-Inyang, Daniel Kaplan, Li Zhou, Zhirong Yao, Qing-Sheng Mi
Source: Frontiers in Immunology, Vol 11 (2020)
Publisher Information: Frontiers Media S.A., 2020.
Publication Year: 2020
Collection: LCC:Immunologic diseases. Allergy
Subject Terms: Langerhans cells, Smad2, Smad3, Smad4, transforming growth factor-β1, Immunologic diseases. Allergy, RC581-607
More Details: Epidermal Langerhans cells (LCs) are skin-resident dendritic cells that are essential for the induction of skin immunity and tolerance. Transforming growth factor-β 1 (TGFβ1) is a crucial factor for LC maintenance and function. However, the underlying TGFβ1 signaling pathways remain unclear. Our previous research has shown that the TGFβ1/Smad3 signaling pathway does not impact LC homeostasis and maturation. In this study, we generated mice with conditional deletions of either individual Smad2, Smad4, or both Smad2 and Smad4 in the LC lineage or myeloid lineage, to further explore the impact of TGFβ1/Smad signaling pathways on LCs. We found that interruption of Smad2 or Smad4 individually or simultaneously in the LC lineage did not significantly impact the maintenance, maturation, antigen uptake, and migration of LCs in vivo or in vitro during steady state. However, the interruption of both Smad2 and Smad4 pathways in the myeloid lineage led to a dramatic inhibition of bone marrow-derived LCs in the inflammatory state. Overall, our data suggest that canonical TGFβ1/Smad2/4 signaling pathways are dispensable for epidermal LC homeostasis and maturation at steady state, but are critical for the long-term LC repopulation directly originating from the bone marrow in the inflammatory state.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-3224
Relation: https://www.frontiersin.org/article/10.3389/fimmu.2020.00912/full; https://doaj.org/toc/1664-3224
DOI: 10.3389/fimmu.2020.00912
Access URL: https://doaj.org/article/90ef1790f09d44b69f950a54308e1f05
Accession Number: edsdoj.90ef1790f09d44b69f950a54308e1f05
Database: Directory of Open Access Journals
More Details
ISSN:16643224
DOI:10.3389/fimmu.2020.00912
Published in:Frontiers in Immunology
Language:English