Institute of Systems Biology, Seattle, WA, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Institute of Systems Biology, Seattle, WA, USA; Molecular Engineering & Sciences Institute, University of Washington, Seattle, WA, USA.
Cell Rep. 2024 Mar 26;43(3):113872. doi: 10.1016/j.celrep.2024.113872. Epub 2024 Feb 29.
Infection, autoimmunity, and cancer are principal human health challenges of the 21 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 (T) 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 T cells. Our results suggest NKG2A biases as a cross-disease factor of protection, supporting suggestions of immunological overlap between infection, autoimmunity, and cancer.
感染、自身免疫和癌症是 21 世纪人类健康的主要挑战。这些疾病通常被认为是免疫学谱的不同末端，但最近的研究表明它们之间可能存在潜在的重叠。例如，炎症在感染和自身免疫中可能具有致病性。驻留记忆 (T) 细胞在感染和癌症中可能有益。然而，这些发现受到规模和范围的限制；确切的免疫因素在疾病之间仍然难以捉摸。在这里，我们整合了 526 名感染患者、162 名狼疮患者和 11180 名癌症患者的大规模深度临床和生物学表型的人类队列。我们确定了一种 NKG2A 免疫偏倚与疾病严重程度、死亡率和自身免疫/急性后慢性疾病的保护相关。我们揭示 NKG2A CD8 T 细胞与炎症减少和体液免疫增加相关，并且它们类似于 T 细胞。我们的结果表明 NKG2A 偏倚是感染、自身免疫和癌症之间保护的跨疾病因素，支持了感染、自身免疫和癌症之间存在免疫学重叠的观点。
