학술논문

Integrative systems biology reveals NKG2A-biased immune responses correlate with protection in infectious disease, autoimmune disease, and cancer
Document Type
article
Source
Cell Reports. 43(3)
Subject
Biological Sciences
Rare Diseases
Autoimmune Disease
Infectious Diseases
Prevention
2.1 Biological and endogenous factors
Aetiology
Inflammatory and immune system
Good Health and Well Being
CD8-Positive T-Lymphocytes
Humans
Communicable Diseases
Neoplasms
Autoimmune Diseases
Inflammation
Autoimmunity
Immunologic Memory
CD8(+) T cells
CP: Immunology
NKG2A
autoimmune disease
cancer
infectious disease
multi-disease
plasma proteomics
single-cell multi-omics
systems immunology
Biochemistry and Cell Biology
Medical Physiology
Biological sciences
Language
Abstract
Infection, autoimmunity, and cancer are principal human health challenges of the 21st century. Often regarded as distinct ends of the immunological spectrum, recent studies hint at potential overlap between these diseases. For example, inflammation can be pathogenic in infection and autoimmunity. T resident memory (TRM) cells can be beneficial in infection and cancer. However, these findings are limited by size and scope; exact immunological factors shared across diseases remain elusive. Here, we integrate large-scale deeply clinically and biologically phenotyped human cohorts of 526 patients with infection, 162 with lupus, and 11,180 with cancer. We identify an NKG2A+ immune bias as associative with protection against disease severity, mortality, and autoimmune/post-acute chronic disease. We reveal that NKG2A+ CD8+ T cells correlate with reduced inflammation and increased humoral immunity and that they resemble TRM cells. Our results suggest NKG2A+ biases as a cross-disease factor of protection, supporting suggestions of immunological overlap between infection, autoimmunity, and cancer.