Tissue-Specific Phenotype and Activation of iNKT Cells in Morbidly Obese Subjects: Interaction with Adipocytes and Effect of Bariatric Surgery
The immune response of visceral adipose tissue (VAT) in obesity, in particular the role of invariant natural killer T (iNKT) cells, has not yet been fully elucidated.
To characterize iNKT cells and its activation status in VAT and peripheral blood mononuclear cells (PBMC) in morbidly obese subjects (MO), and to analyze their association with metabolic parameters.
Subjects and Methods
Twenty non-obese and 20 MO subjects underwent Roux-en-Y gastric bypass (RYGB) and were studied before and 6 months after RYGB. VAT and PBMC were obtained.
A decrease in VAT iNKT cells from MO was found, however, not in PBMC. Visceral adipocytes from MO presented increased CD1d expression (p = 0.032). MO presented an increase in early activated CD69+ iNKT cells in PBMC before RYGB (p < 0.001), but not after RYGB nor in VAT, and an increase in later activated CD25+ iNKT in VAT (p = 0.046), without differences in PBMC. The co-expression of early and later markers (CD69+CD25+) in iNKT cells was increased in MO in VAT (p = 0.050) and PBMC (p = 0.006), decreasing after RYGB (p = 0.050). CD69+ iNKT and CD69+CD25+ iNKT cells in PBMC after RYGB correlated negatively with glucose, insulin, and insulin resistance levels.
There is a tissue-specific phenotype and activation of iNKT cells in VAT in morbid obesity, which could be involved in VAT immunometabolism dysregulation. Also, the increase in CD1d expression could be to offset the lack of VAT iNKT cells.
KeywordsNatural killer T cells Inflammation Obesity Adipose tissue
CIBERObn is an ISCIII project. We gratefully acknowledge the Imaging platform of the Institute of Biomedical Research in Malaga (IBIMA), as well as the technical assistance from Gomez-Conde, AI.
This study has been supported by the Instituto de Salud Carlos III (ISCIII) (PI09/01016) (“A way to make Europe”), the Andalusian Ministry of Health (PI-2013-575), and the Andalusian Ministry of Economy, Science and Innovation (P10-CTS6928, P11-CTS8161 and P11-CTS8081) and co-financed by the European Regional Development Fund (FEDER) (“Andalusia moves with Europe”).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no competing interests.
- 18.Reddy M, Eirikis E, Davis C, et al. Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function. J Immunol Methods. 2004;293:127–42.CrossRefPubMedGoogle Scholar