Project description:The central nervous system (CNS), despite the presence of strategically positioned anatomical barriers designed to protect it, is not entirely isolated from the immune system. In fact, it remains physically connected to and can be influenced by the peripheral immune system. How the CNS retains such responsiveness while maintaining “immune privilege” remains an outstanding conundrum. In searching for molecular cues that derive from the CNS and allow its direct communication with the immune system, we discovered a repertoire of CNS-derived endogenous guardian peptides presented on major histocompatibility complex (MHC) II molecules at the CNS borders. During homeostasis, a preponderance of these guardian peptides were found to be bound to MHC II molecules throughout the path of lymphatic drainage from the brain to its surrounding meninges and its draining cervical lymph nodes. With neuroinflammatory disease, however, the presentation of guardian peptides was diminished. Fascinatingly, boosting the presence of these guardian peptides reinforced a population of suppressor CD4+ T cells and significantly reduced CNS autoimmune disease. This unexpected discovery of CNS-derived autoimmune guardian peptides may be the molecular key adapting the CNS to receive information and to maintain continuous dialogue with the immune system while balancing overt autoreactivity. This sheds new light on how we conceptually think about and therapeutically target neuroinflammatory and neurodegenerative diseases.

2024-10-11 | GSE240691 | GEO

NIDDM-Atherosclerosis Study (NIDDM-Athero)

Project description:<p>The NIDDM-Atherosclerosis Study, funded by NHLBI, was designed as a family study to examine the genetic basis of subclinical atherosclerosis and diabetes in Hispanic families. Family members of probands with T2D were recruited in the Los Angeles area. The baseline examination of the cohort included the euglycemic hyperinsulinemic clamp test from which the two key phenotypes were obtained: insulin sensitivity (M) and metabolic clearance rate of insulin (MCRI). Genome-wide genotyping was obtained under separate funding by NIDDK as a part of the GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium.</p>

| phs001130 | dbGaP

GUARDIAN: IRAS (IRAS Classic)

Project description:<p>The Insulin Resistance Atherosclerosis Study (IRAS) was an epidemiologic cohort study designed to examine the relationship between insulin resistance and carotid atherosclerosis across a range of glucose tolerance. Individuals of self-reported Mexican-American ethnicity were recruited in San Antonio, TX and San Luis Valley, CO. Recruitment was balanced across age and glucose tolerance status. GUARDIAN includes 173 individuals from the IRAS. Insulin sensitivity was obtained by FSIGT.</p>

| phs001014 | dbGaP

GUARDIAN: Mexican-American Coronary Artery Disease Study (MACAD)

Project description:GUARDIAN: Mexican-American Coronary Artery Disease Study (MACAD)

| PRJNA392714 | ENA

Homo sapiens

Project description:GUARDIAN: Insulin Resistance and Atherosclerosis Study (IRAS)

| PRJNA300463 | ENA