Obesity, which is an epidemic in the United States, increases the risk of developing cancer. Recently, it has been determined that obesity is associated with chronic low-grade inflammation that requires elements of the immune system. In our preliminary data we find that obese people have a Thelper (TH)22/TH17 signature in blood and adipose tissue, most likely linked to the ongoing inflammation. Interleukin-22 (IL-22) has important proliferative and wound-healing properties on epithelial and stromal cells necessary to maintain homeostasis at mucosal sites. However, we postulate that persistent IL-22 secretion may drive uncontrolled epithelial proliferation and tumor development. IL-22 in adaptive and innate cells is under the control of a transcription factor known as Aryl Hydrocarbon Receptor (AHR). AHR signaling is activated by endogenous ligands but also by diet-associated compounds and environmental products. We plan to test the hypothesis that AHR signaling may favor cancer development in obesity by potentiating IL-22 production. These studies may open new avenues of therapeutic intervention through diet to prevent cancer associated to obesity.
Obesity is constantly rising in the United States and soon 20% of the adult population will be obese. Obesity has devastating consequences on people general health. Obesity increases the risk of diabetes, heart disease, and atherosclerosis and increases the chances of developing cancer. In the last years it became evident that white cells of the blood and organs, which normally fight viral and bacterial infections, are also important to attenuate or worsen obesity and its consequences. In this grant application we propose to study whether a new recently discovered pathway modulating the secretion of some soluble mediators from white blood cells is involved in obesity. We hypothesize that this pathway that detects environmental triggers, in the context of a high calorie, high fat Western diet aggravates obesity and obesity-associated risk of developing cancer.
| Bando, Jennifer K; Gilfillan, Susan; Song, Christina et al. (2018) The Tumor Necrosis Factor Superfamily Member RANKL Suppresses Effector Cytokine Production in Group 3 Innate Lymphoid Cells. Immunity 48:1208-1219.e4 |
| Robinette, M L; Cella, M; Telliez, J B et al. (2018) Jak3 deficiency blocks innate lymphoid cell development. Mucosal Immunol 11:50-60 |
| Cortez, Victor S; Ulland, Tyler K; Cervantes-Barragan, Luisa et al. (2017) SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-? signaling. Nat Immunol 18:995-1003 |
| Costa, Maria Laura; Robinette, Michelle L; Bugatti, Mattia et al. (2017) Two Distinct Myeloid Subsets at the Term Human Fetal-Maternal Interface. Front Immunol 8:1357 |
| Cervantes-Barragan, Luisa; Chai, Jiani N; Tianero, Ma Diarey et al. (2017) Lactobacillus reuteri induces gut intraepithelial CD4+CD8??+ T cells. Science 357:806-810 |
| Koues, Olivia I; Collins, Patrick L; Cella, Marina et al. (2016) Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells. Cell 165:1134-1146 |
| Cortez, Victor S; Cervantes-Barragan, Luisa; Robinette, Michelle L et al. (2016) Transforming Growth Factor-? Signaling Guides the Differentiation of Innate Lymphoid Cells in Salivary Glands. Immunity 44:1127-39 |
| Cella, Marina; Colonna, Marco (2015) Aryl hydrocarbon receptor: Linking environment to immunity. Semin Immunol 27:310-4 |
| Song, Christina; Lee, Jacob S; Gilfillan, Susan et al. (2015) Unique and redundant functions of NKp46+ ILC3s in models of intestinal inflammation. J Exp Med 212:1869-82 |
| Cella, Marina; Miller, Hannah; Song, Christina (2014) Beyond NK cells: the expanding universe of innate lymphoid cells. Front Immunol 5:282 |
