A cellular census of human peripheral immune cells identifies novel cell states in lung diseases

Abstract

Increasing evidence supports a central role of the immune system in lung diseases. Understanding how immunological alterations between lung diseases provide opportunities for immunotherapy. Exhausted T cells play a key role of immune suppression in lung cancer and chronic obstructive pulmonary disease was proved in our previous study. The present study aims to furthermore define molecular landscapes and heterogeneity of systemic immune cell target proteomic and transcriptomic profiles and interactions between circulating immune cells and lung residential cells in various lung diseases. We firstly measured target proteomic profiles of circulating immune cells from healthy volunteers and patients with stable pneumonia, stable asthma, acute asthma, acute exacerbation of chronic obstructive pulmonary disease, chronic obstructive pulmonary disease and lung cancer, using single‐cell analysis by cytometry by time‐of‐flight with 42 antibodies. The nine immune cells landscape was mapped among those respiratory system diseases, including CD4 + T cells, CD8 + T cells, dendritic cells, B cells, eosinophil, γδT cells, monocytes, neutrophil and natural killer cells. The double‐negative T cells and exhausted CD4 + central memory T cells subset were identified in patients with acute pneumonia. This T subset expressed higher levels of T‐cell immunoglobulin and mucin domain‐containing protein 3 (Tim3) and T‐cell immunoreceptor with Ig and ITIM domains (TIGIT) in patients with acute pneumonia and stable pneumonia. Biological processes and pathways of immune cells including immune response activation, regulation of cell cycle and pathways in cancer in peripheral blood immune cells were defined by bulk RNA sequencing (RNA‐seq). The heterogeneity among immune cells including CD4 + , CD8 + T cells and NK T cells by single immune cell RNA‐seq with significant difference was found by single‐cell sequencing. The effect of interstitial telocytes on the immune cell types and immune function was finally studied and the expressions of CD8a and chemokine C–C motif receptor 7 (CCR7) were increased significantly in co‐cultured groups. Our data indicate that proteomic and transcriptomic profiles and heterogeneity of circulating immune cells provides new insights for understanding new molecular mechanisms of immune cell function, interaction and modulation as a source to identify and develop biomarkers and targets for lung diseases.

How to translate the knowledge of COVID‐19 into the prevention of Omicron variants

“…It will be even more complex if the number and location of mutations of Omicron variants dynamically change along with the duration, human races, individuals, and therapy and modify during the replication and binding, to rapidly increase the capacity of infections. We should closely monitor new clusters and functions of circulating immune cells as well as the difference of biological processes and pathways as reported in COVIN‐19 and lung diseases, 11 , 12 when we emphasize accelerating the surveillance and sequencing processes of SARS‐CoV‐2 variants. We recently proposed that the single‐cell RNA sequencing of circulating immune cells could be applied as a routine approach of clinical biochemistry to better understand the response of patients with the disease and the role of circulating immune cell involvement.…”

Circulating T Cell Activation and Exhaustion Markers Are Associated With Radiation Pneumonitis and Poor Survival in Non-Small-Cell Lung Cancer

“…T cell activation is typical in both cancer progression ( 36 ), among others, in NSCLC ( 37 , 38 ) and pneumonitis ( 39 ) due to persistent T cell receptor stimulation and is accompanied by the expression of inhibitory receptors such as PD-1 and TIM-3 ( 40 – 42 ) and T cell dysfunction ( 40 ). At the same time, radiotherapy modulates several immunological processes: revelation of antigens, activation of T lymphocytes, recruitment and accumulation of T cells in the tumour, and acknowledgement and killing of tumour cells by T lymphocytes.…”

Forward single‐cell sequencing into clinical application: Understanding of ageing and rejuvenation from clinical observation to single‐cell solution

“…One of Clinical and Translational Medicine's missions is to advance spatiotemporal molecular medicine by advancing single‐cell sequencing into clinical application, translating single‐cell measurements into routine practice, and identifying disease‐specific biomarkers and therapies 4–6 . Advanced technologies such as single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics have broad applications in clinical tissue or fluid samples to understand intra‐ and intercellular communications and network interactions within the tissue or within the circulation 7–10 . The current Editorial extends our understanding of ageing and rejuvenation from clinical observation in clinical and translational medicine to molecular mechanisms of heterochronic parabiosis at single‐cell solution (Figure 1).…”

“…[4][5][6] Advanced technologies such as single-cell RNA sequencing (scRNAseq) and spatial transcriptomics have broad applications in clinical tissue or fluid samples to understand intraand intercellular communications and network interactions within the tissue or within the circulation. [7][8][9][10] The current Editorial extends our understanding of ageing and rejuvenation from clinical observation in clinical and translational medicine to molecular mechanisms of heterochronic parabiosis at single-cell solution (Figure 1). The Editorial calls special attention to the identification and development of ageing-associated and specific biomarkers and targets that may impact ageing metabolism, molecular regulation and genetic alteration.…”