TY - JOUR
T1 - High-Fat Diet Rapidly Modifies Trafficking, Phenotype, and Function of Plasmacytoid Dendritic Cells in Adipose Tissue
AU - Stutte, Susanne
AU - Ishikawa-Ankerhold, Hellen
AU - Lynch, Lydia
AU - Eickhoff, Sarah
AU - Nasiscionyte, Simona
AU - Guo, Chenglong
AU - Heuvel, Dominic van den
AU - Setzensack, Daniel
AU - Colonna, Marco
AU - Maier-Begandt, Daniela
AU - Weckbach, Ludwig
AU - Brocker, Thomas
AU - Schulz, Christian
AU - Walzog, Barbara
AU - von Andrian, Ulrich
N1 - Publisher Copyright:
Copyright © 2022 by The American Association of Immunologists, Inc. 0022-1767/22/$37.50
PY - 2022/3/15
Y1 - 2022/3/15
N2 - Plasmacytoid dendritic cells (pDCs) display an increased abundance in visceral adipose tissue (VAT) of humans with obesity. In the current study, we set out to decipher the molecular mechanisms of their recruitment to VAT and the functional relevance of this process. We observed increased pDC numbers in murine blood, liver, spleen, and VAT after feeding a high-fat diet (HFD) for 3 wk when compared with a standard diet. pDCs were enriched in fat-associated lymphoid clusters representing highly specific lymphoid regions within VAT. HFD led to an enlargement of fat-associated lymphoid clusters with an increased density and migratory speed of pDCs as shown by intravital multiphoton microscopy. For their recruitment into VAT, pDCs employed P-selectin with E-selectin and L-selectin being only critical in response to HFD, indicating that the molecular cues underlying pDC trafficking were dependent on the nutritional state. Subsequent recruitment steps required a4b1 and a4b7 integrins and engagement of CCR7. Application of fingolimod (FTY720) abrogated egress of pDCs from VAT, indicating the involvement of sphingosine-1-phosphate in this process. Furthermore, HFD altered pDC functions by promoting their activation and type 1 IFN expression. Blocking pDC infiltration into VAT prevented weight gain and improved glucose tolerance during HFD. In summary, a HFD fundamentally alters pDC biology by promoting their trafficking, retention, and activation in VAT, which in turn seems to regulate metabolism. The Journal of Immunology, 2022, 208: 1445-1455.
AB - Plasmacytoid dendritic cells (pDCs) display an increased abundance in visceral adipose tissue (VAT) of humans with obesity. In the current study, we set out to decipher the molecular mechanisms of their recruitment to VAT and the functional relevance of this process. We observed increased pDC numbers in murine blood, liver, spleen, and VAT after feeding a high-fat diet (HFD) for 3 wk when compared with a standard diet. pDCs were enriched in fat-associated lymphoid clusters representing highly specific lymphoid regions within VAT. HFD led to an enlargement of fat-associated lymphoid clusters with an increased density and migratory speed of pDCs as shown by intravital multiphoton microscopy. For their recruitment into VAT, pDCs employed P-selectin with E-selectin and L-selectin being only critical in response to HFD, indicating that the molecular cues underlying pDC trafficking were dependent on the nutritional state. Subsequent recruitment steps required a4b1 and a4b7 integrins and engagement of CCR7. Application of fingolimod (FTY720) abrogated egress of pDCs from VAT, indicating the involvement of sphingosine-1-phosphate in this process. Furthermore, HFD altered pDC functions by promoting their activation and type 1 IFN expression. Blocking pDC infiltration into VAT prevented weight gain and improved glucose tolerance during HFD. In summary, a HFD fundamentally alters pDC biology by promoting their trafficking, retention, and activation in VAT, which in turn seems to regulate metabolism. The Journal of Immunology, 2022, 208: 1445-1455.
UR - http://www.scopus.com/inward/record.url?scp=85126072822&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.2100022
DO - 10.4049/jimmunol.2100022
M3 - Article
C2 - 35181637
AN - SCOPUS:85126072822
SN - 0022-1767
VL - 208
SP - 1445
EP - 1455
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -