| Autor: |
Jing Wang, Qiyao Chai, Zehui Lei, Yiru Wang, Jiehua He, Pupu Ge, Zhe Lu, Lihua Qiang, Dongdong Zhao, Shanshan Yu, Changgen Qiu, Yanzhao Zhong, Bing-Xi Li, Lingqiang Zhang, Yu Pang, George Fu Gao, Cui Hua Liu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
EMBO Molecular Medicine, Vol 16, Iss 8, Pp 1755-1790 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1757-4684 |
| DOI: |
10.1038/s44321-024-00106-1 |
| Popis: |
Abstract Chronic infections, including Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), can induce host immune exhaustion. However, the key checkpoint molecules involved in this process and the underlying regulatory mechanisms remain largely undefined, which impede the application of checkpoint-based immunotherapy in infectious diseases. Here, through adopting time-of-flight mass cytometry and transcriptional profiling to systematically analyze natural killer (NK) cell surface receptors, we identify leukocyte immunoglobulin like receptor B1 (LILRB1) as a critical checkpoint receptor that defines a TB-associated cell subset (LILRB1+ NK cells) and drives NK cell exhaustion in TB. Mechanistically, Mtb-infected macrophages display high expression of human leukocyte antigen-G (HLA-G), which upregulates and activates LILRB1 on NK cells to impair their functions by inhibiting mitogen-activated protein kinase (MAPK) signaling via tyrosine phosphatases SHP1/2. Furthermore, LILRB1 blockade restores NK cell-dependent anti-Mtb immunity in immuno-humanized mice. Thus, LILRB1-HLA-G axis constitutes a NK cell immune checkpoint in TB and serves as a promising immunotherapy target. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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