Details

Autor(en) / Beteiligte

• Luck, Helen
• Khan, Saad
• Kim, Justin H
• Copeland, Julia K
• Revelo, Xavier S
• Tsai, Sue
• Chakraborty, Mainak
• Cheng, Kathleen
• Tao Chan, Yi
• Nøhr, Mark K
• Clemente-Casares, Xavier
• Perry, Marie-Christine
• Ghazarian, Magar
• Lei, Helena
• Lin, Yi-Hsuan
• Coburn, Bryan
• Okrainec, Allan
• Jackson, Timothy
• Poutanen, Susan
• Gaisano, Herbert
• Allard, Johane P
• Guttman, David S
• Conner, Margaret E
• Winer, Shawn
• Winer, Daniel A

Titel

Gut-associated IgA + immune cells regulate obesity-related insulin resistance

Ist Teil von

• Nature communications, 2019-08, Vol.10 (1), p.3650-17, Article 3650

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• The intestinal immune system is emerging as an important contributor to obesity-related insulin resistance, but the role of intestinal B cells in this context is unclear. Here, we show that high fat diet (HFD) feeding alters intestinal IgA immune cells and that IgA is a critical immune regulator of glucose homeostasis. Obese mice have fewer IgA immune cells and less secretory IgA and IgA-promoting immune mediators. HFD-fed IgA-deficient mice have dysfunctional glucose metabolism, a phenotype that can be recapitulated by adoptive transfer of intestinal-associated pan-B cells. Mechanistically, IgA is a crucial link that controls intestinal and adipose tissue inflammation, intestinal permeability, microbial encroachment and the composition of the intestinal microbiome during HFD. Current glucose-lowering therapies, including metformin, affect intestinal-related IgA B cell populations in mice, while bariatric surgery regimen alters the level of fecal secretory IgA in humans. These findings identify intestinal IgA immune cells as mucosal mediators of whole-body glucose regulation in diet-induced metabolic disease.