Scientific Publications by FDA Staff

Diabetes 2018 Aug;67(8):1589-603

TACI deficient macrophages protect mice against metaflammation and obesity-induced dysregulation of glucose homeostasis.

Liu L, Inouye KE, Allman WR, Coleman AS, Siddiqui S, Hotamisligil GS, Akkoyunlu M

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 (Mvarphis), eosinophils and type 2 innate lymphoid cells in visceral adipose tissue (VAT) is implicated in the protection from obesity induced assaults. Supporting this hypothesis, adoptively transferred TACI-deficient peritoneal or AT Mvarphis, but not B cells, can improve glucose metabolism in the obese host. Interestingly, not only the transferred TACI-deficient Mvarphis home to host VAT but also trigger the accumulation of host M2 Mvarphis and eosinophils in VAT. The increase in host M2 Mvarphis in VAT is likely a result of eosinophil recruitment in response to eotaxin-2 produced by TACI-deficient Mvarphis. Insulin signaling experiments revealed that IL-10 secreted by TACI-deficient Mvarphis is responsible for maintaining adipocyte insulin sensitivity. Thus, the adoptive transfer experiments offer a model where TACI-deficient Mvarphis accumulate in VAT and protect against metaflammation and obesity-associated dysregulation of glucose metabolism.