| First Author | Efimova I | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 643144 | PubMed ID | 33717200 |
| Mgi Jnum | J:316688 | Mgi Id | MGI:6807215 |
| Doi | 10.3389/fimmu.2021.643144 | Citation | Efimova I, et al. (2021) GIPR Signaling in Immune Cells Maintains Metabolically Beneficial Type 2 Immune Responses in the White Fat From Obese Mice. Front Immunol 12:643144 |
| abstractText | Glucose-dependent insulinotropic polypeptide (GIP) communicates information on energy availability from the gut to peripheral tissues. Disruption of its signaling in myeloid immune cells during high-fat diet (HFD)-induced obesity impairs energy homeostasis due to the unrestrained metabolically deleterious actions of S100A8/A9 alarmin. White adipose tissue (WAT) type 2 immune cell networks are important for maintaining metabolic and energy homeostasis and limiting obesity-induced inflammation. Nevertheless, the consequences of losing immune cell GIP receptor (GIPR) signaling on type 2 immunity in WAT remains unknown. Bone marrow (BM) chimerism was used to generate mice with GIPR (Gipr(-/-) BM) and GIPR/S100A8/A9 (Gipr(-/-) /S100a9(-/-) BM) deletion in immune cells. These mice were subjected to short (5 weeks) and progressive (14 weeks) HFD regimens. GIPR-deficiency was also targeted to myeloid cells by crossing Gipr(fl/fl) mice and Lyz2(cre/+) mice (LysM(DeltaGipr) ). Under both short and progressive HFD regimens, Gipr(-/-) BM mice exhibited altered expression of key type 2 immune cytokines in the epididymal visceral WAT (epiWAT), but not in subcutaneous inguinal WAT. This was further linked to declined representation of type 2 immune cells in epiWAT, such as group 2 innate lymphoid cells (ILC2), eosinophils, and FOXP3(+) regulatory T cells (Tregs). Co-deletion of S100A8/A9 in Gipr(-/-) immune cells reversed the impairment of type 2 cytokine expression in epiWAT, suggesting a mechanistic role for this alarmin in type 2 immune suppression. LysM(DeltaGipr) mice on HFD also displayed altered expression of type 2 immune mediators, highlighting that GIPR-deficiency in myeloid immune cells is responsible for the impairment of type 2 immune networks. Finally, abrogated GIPR signaling in immune cells also affected adipocyte fraction cells, inducing their increased production of the beiging interfering cytokine IL-10 and stress- related type 2 cytokine IL-13. Collectively, these findings attribute an important role for GIPR in myeloid immune cells in supporting WAT type 2 immunity. |
