Document text
Principal Investigator: DJURDJICA COSS
Organization: UNIVERSITY OF CALIFORNIA RIVERSIDE
Fiscal Year: 2024
Award: $226,121
Funding agency: National Institute of Allergy and Infectious Diseases
Obesity incidence is increasing worldwide with the urgent need to identify new therapeutics.
Increased adiposity is associated with chronic inflammation, which can exacerbate a number of
obesity-associated diseases, including COVID-19 infection and allergic disease. There are
profound sex differences in immune cell activation driving obesity-mediated pathologies.
However, there remain critical gaps in knowledge on the immune mechanisms underlying
obesity, and whether they are sexually dimorphic. Preliminary data generated from transgenic
mice, adoptive immune cell transfer, and adipose single cell sequencing uncovered a new
RELMα-eosinophil-macrophage axis that is female-specific and protective in obesity and
associated inflammation. Transcriptomic profiling of the adipose macrophages identified novel
sex-specific and RELMα-dependent genes such as chemokines, hemoglobins and a long non-
coding RNA (lncRNA) as new molecular candidates to treat obesity. Based on these findings,
the overarching goal of this study is to investigate sexual dimorphism in innate immune cell
crosstalk in obesity, from how gonadal hormones direct macrophage-eosinophil interaction (Aim
1) to determining downstream effectors in macrophages, such as hemoglobins and lncRNA, and
their mechanisms of action associated with oxidative stress in the obese adipose tissues (Aim
2). Strengths of the proposed study include the multidisciplinary nature of the experimental
design, which combines the co-PIs expertise in reproductive endocrinology and innate immunity,
and the public health impact of investigating the understudied area of sex differences and how
they may guide more specific treatments for obesity and associated risks for infection and
allergic disease.
Terms: <21+ years old><Adipose tissue><Adult><Adult Human><Adult-Onset Diabetes Mellitus><Affect><Allergic Disease><Allergy><Area><Automobile Driving><Blood Eosinophil><Body Tissues><COVID-19 infection><COVID-19 virus infection><COVID19 infection><Cell Body><Cells><Chemotactic Cytokines><Chronic><Co-culture><Cocultivation><Coculture><Coculture Techniques><Data><Diagnosis><Differences between sexes><Differs between sexes><Disease><Disorder><Endocrine><Endocrinology><Environment><Eosinophilic Granulocyte><Eosinophilic Leukocyte><Epidemic><Estrogens><Experimental Designs><Fatty Tissue><Feedback><Female><Femara><Functional RNA><Future><Genes><Goals><Gonadal Hormones><Gonadal Steroid Hormones><Grant><Hemoglobin><Heterogeneity><Homologous Chemotactic Cytokines><Hypersensitivity><Immune><Immune Cell Activation><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune response><Immunes><Immunodeficiency and Immunosuppression Disorders><Immunologic Diseases><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Immunological response><Immunology><Incidence><Infection><Inflammation><Inflammatory><Inflammatory Response><Innate Immune Response><Innate Immunity><Intercrines><Investigation><KO mice><Ketosis-Resistant Diabetes Mellitus><Knock-out Mice><Knockout Mice><Knowledge><Letrozole><Link><Macrophage><Marrow Eosinophil><Maturity-Onset Diabetes Mellitus><Mediating><Metabolism and Endocrinology><Mice><Mice Mammals><Molecular><Murine><Mus><Mφ><NIDDM><Native Immunity><Natural Immunity><Nature><Non-Coding><Non-Coding RNA><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Non-Specific Immunity><Non-translated RNA><Noncoding RNA><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Nonspecific Immunity><Nontranslated RNA><Null Mouse><Obesity><Obesity associated disease><Obesity related disease><Oophorectomy><Operative Procedures><Operative Surgical Procedures><Ovariectomy><Oxidative Stress><Pathogenesis><Pathology><Pathway interactions><Process><Proteins><Public Health><Publishing><Regulation><Reproductive Endocrinology><Risk><SARS-CoV-2 infection><SARS-CoV2 infection><SIS cytokines><Severe acute respiratory syndrome coronavirus 2 infection><Sex Differences><Sex Hormones><Sex Steroid Hormones><Sexual differences><Single cell seq><Slow-Onset Diabetes Mellitus><Stable Diabetes Mellitus><Surgical><Surgical Interventions><Surgical Procedure><T2 DM><T2D><T2DM><Testing><Therapeutic Estrogen><Tissues><Transcript><Transgenic Mice><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><United States><Untranslated RNA><adipose><adiposity><adult onset diabetes><adulthood><cell type><chemoattractant cytokine><chemokine><co-morbid><co-morbidity><comorbidity><coronavirus disease 2019 infection><corpulence><driving><eosinophil><estrogen disrupting><estrogen disruption><estrogenic disruption><female gonadectomy><gonadal steroids><high risk><host response><immune activation><immune system response><immunoresponse><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><infection risk><innate immune pathways><ketosis resistant diabetes><male><maturity onset diabetes><multidisciplinary><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><noncoding><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><obese individuals><obese people><obese person><obese population><obese subjects><obesity intervention><obesity therapy><obesity treatment><overexpress><overexpression><pathway><pharmacologic><pre-clinical><pre-clinical study><preclinical><preclinical study><public health relevance><response><scRNA-seq><sex><sex based differences><sex dimorphism><sex steroid><sex-dependent differences><sex-related differences><sex-specific differences><sexual dimorphism><sexually dimorphic><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell next generation sequencing><single cell sequencing><single cell transcriptomic profiling><single-cell RNA sequencing><surgery><transcriptome profiling><transcriptomic profiling><transcriptomics><type 2 DM><type II DM><type two diabetes><white adipose tissue><yellow adipose tissue>