TACI-Deficient Macrophages Protect Mice Against Metaflammation and Obesity-Induced Dysregulation of Glucose Homeostasis

Diabetes. 2018 Aug;67(8):1589-1603. doi: 10.2337/db17-1089. Epub 2018 Jun 5.


Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is a receptor for the TNF superfamily cytokines, B cell-activating factor (BAFF), and A proliferation-inducing ligand (APRIL). Here, we demonstrate that TACI-deficient mice subjected to high-fat diet (HFD) are protected from weight gain and dysregulated glucose homeostasis. Resistance to HFD-induced metabolic changes in TACI-deficient mice does not involve TACI-mediated adipogenesis. Instead, accumulation of M2 macrophages (Mϕs), eosinophils, and type 2 innate lymphoid cells in visceral adipose tissue (VAT) is implicated in the protection from obesity-induced assaults. In support of this hypothesis, adoptively transferred TACI-deficient peritoneal or adipose tissue Mϕs, but not B cells, can improve glucose metabolism in the obese host. Interestingly, the transferred TACI-deficient Mϕs not only home to host VAT but also trigger the accumulation of host M2 Mϕs and eosinophils in VAT. The increase in host M2 Mϕs in VAT is likely a result of eosinophil recruitment in response to eotaxin-2 produced by TACI-deficient Mϕs. Insulin signaling experiments revealed that IL-10 secreted by TACI-deficient Mϕs is responsible for maintaining adipocyte insulin sensitivity. Thus, the adoptive transfer experiments offer a model where TACI-deficient Mϕs accumulate in VAT and protect against metaflammation and obesity-associated dysregulation of glucose metabolism.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity*
  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Cells, Cultured
  • Diet, High-Fat / adverse effects
  • Female
  • Gene Expression Regulation
  • Glucose Intolerance / etiology
  • Glucose Intolerance / immunology
  • Glucose Intolerance / prevention & control*
  • Immunotherapy, Adoptive*
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism
  • Insulin Resistance
  • Intra-Abdominal Fat / immunology*
  • Intra-Abdominal Fat / metabolism
  • Intra-Abdominal Fat / pathology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Macrophages / transplantation*
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / pathology
  • Macrophages, Peritoneal / transplantation
  • Mice
  • Mice, Knockout
  • Obesity / metabolism
  • Obesity / pathology
  • Obesity / physiopathology
  • Obesity / therapy*
  • RNA Interference
  • Transmembrane Activator and CAML Interactor Protein / antagonists & inhibitors
  • Transmembrane Activator and CAML Interactor Protein / chemistry
  • Transmembrane Activator and CAML Interactor Protein / genetics
  • Transmembrane Activator and CAML Interactor Protein / metabolism*
  • Weight Gain


  • Biomarkers
  • Inflammation Mediators
  • Tnfrsf13b protein, mouse
  • Transmembrane Activator and CAML Interactor Protein