The Role of Innate Lymphoid Cells in the Regulation of Immune Homeostasis in Sepsis-Mediated Lung Inflammation

Akama, Yuichi; Satoh-Takayama, Naoko; Kawamoto, Eiji; Ito, Atsushi; Gaowa, Arong; Park, Eun Jeong; Imai, Hiroshi; Shimaoka, Motomu

doi:10.3390/diagnostics10100808

Cited by 10 publications

(7 citation statements)

References 95 publications

(105 reference statements)

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“…The roles of ILC2s in the lung inflammation induced by sepsis have been reported. ILC2, the most abundant ILC subset in the lungs, secretes type 2 cytokines such as IL-5 and IL-13, thereby playing the important roles in the regulation of type 2 immune responses, which is required for resolving inflammation and remodeling tissues ( 110 ). Insufficient resolution of inflammation and aberrant regulation of tissue repair and remodeling causes acute lung injury (ALI), and lung fibrosis, leading to the irreversible destruction of pulmonary functions.…”

Section: Pd-1/pd-l As a Novel Therapeutic Target To Reverse Immune Pamentioning

confidence: 99%

Immune Deregulation in Sepsis and Septic Shock: Reversing Immune Paralysis by Targeting PD-1/PD-L1 Pathway

2021

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Sepsis remains a major problem for human health worldwide, thereby manifesting high rates of morbidity and mortality. Sepsis, once understood as a monophasic sustained hyperinflammation, is currently recognized as a dysregulated host response to infection, with both hyperinflammation and immunoparalysis occurring simultaneously from the earliest stages of sepsis, involving multiple organ dysfunctions. Despite the recent progress in the understanding of the pathophysiology underlying sepsis, no specific treatment to restore immune dysregulation in sepsis has been validated in clinical trials. In recent years, treatment for immune checkpoints such as the programmed cell death protein 1/programmed death ligand (PD-1/PD-L) pathway in tumor-infiltrating T-lymphocytes has been successful in the field of cancer immune therapy. As immune-paralysis in sepsis involves exhausted T-lymphocytes, future clinical applications of checkpoint inhibitors for sepsis are expected. In addition, the functions of PD-1/PD-L on innate lymphoid cells and the role of exosomal forms of PD-L1 warrant further research. Looking back on the history of repeatedly failed clinical trials of immune modulatory therapies for sepsis, sepsis must be recognized as a difficult disease entity for performing clinical trials. A major obstacle that could prevent effective clinical trials of drug candidates is the disease complexity and heterogeneities; clinically diagnosed sepsis could contain multiple sepsis subgroups that suffer different levels of hyper-inflammation and immune-suppression in distinct organs. Thus, the selection of appropriate more homogenous sepsis subgroup is the key for testing the clinical efficacy of experimental therapies targeting specific pathways in either hyperinflammation and/or immunoparalysis. An emerging technology such as artificial intelligence (AI) may help to identify an immune paralysis subgroup who would best be treated by PD-1/PD-L1 pathway inhibitors.

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Section: Pd-1/pd-l As a Novel Therapeutic Target To Reverse Immune Pamentioning

confidence: 99%

Immune Deregulation in Sepsis and Septic Shock: Reversing Immune Paralysis by Targeting PD-1/PD-L1 Pathway

2021

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“…Recently a small subset of other immune cells was identified in the lung, namely, innate lymphoid cells (ILCs), which are distinct from T and B lymphocytes. ILC1s, ILC2s, and ILC3s act as the innate counterparts of the traditional Th (CD4 + T helper) 1, Th2, and Th17 T cell effector subsets, respectively [ 1 ]. Furthermore, ILCs and traditional T cells also share a common ontogeny [ 2 – 4 ].…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between ILC2s and Th2 CD4+ T Cells in Lung Disease

Guo

2022

Journal of Immunology Research

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Cytokine secretion, such as interleukin-4 (IL-4), IL-5, IL-9, IL-13, and amphiregulin (Areg), by type 2 innate lymphoid cells (ILC2s) is indispensable for homeostasis, remodeling/repairing tissue structure, inflammation, and tumor immunity. Often viewed as the innate cell surrogate of T helper type 2 (Th2) cells, ILC2s not only secrete the same type 2 cytokines, but are also inextricably related to CD4+T cells in terms of cell origin and regulatory factors, bridging between innate and adaptive immunity. ILC2s interact with CD4+T cells to play a leading role in a variety of diseases through secretory factors. Here, we review the latest progress on ILC2s and CD4+T cells in the lung, the close relationship between the two, and their relevance in the lung disease and immunity. This literature review aids future research in pulmonary type 2 immune diseases and guides innovative treatment approaches for these diseases.

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“…Previous studies have shown that ILC2 plays an important role in regulating adaptive immunity, macrophage polarization, etc ( 27 , 28 ). The results of the Go enrichment analysis ( Figure 4F ) showed that DEGs of ILC2 were mainly focused on regulating innate immune cells, including regulating the myeloid cell differentiation, and positive regulation of cytokine ( 18 ).…”

Section: Resultsmentioning

confidence: 99%

Integrating bulk and single-cell sequencing reveals the phenotype-associated cell subpopulations in sepsis-induced acute lung injury

Wang

Chen

et al. 2022

Front. Immunol.

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The dysfunctional immune response and multiple organ injury in sepsis is a recurrent theme impacting prognosis and mortality, while the lung is the first organ invaded by sepsis. To systematically elucidate the transcriptomic changes in the main constituent cells of sepsis-injured lung tissue, we applied single-cell RNA sequencing to the lung tissue samples from septic and control mice and created a comprehensive cellular landscape with 25044 cells, including 11317 immune and 13727 non-immune cells. Sepsis alters the composition of all cellular compartments, particularly neutrophils, monocytes, T cells, endothelial, and fibroblasts populations. Our study firstly provides a single-cell view of cellular changes in septic lung injury. Furthermore, by integrating bulk sequencing data and single-cell data with the Scissors-method, we identified the cell subpopulations that are most associated with septic lung injury phenotype. The phenotypic-related cell subpopulations identified by Scissors-method were consistent with the cell subpopulations with significant composition changes. The function analysis of the differentially expressed genes (DEGs) and the cell-cell interaction analysis further reveal the important role of these phenotype-related subpopulations in septic lung injury. Our research provides a rich resource for understanding cellular changes and provides insights into the contributions of specific cell types to the biological processes that take place during sepsis-induced lung injury.

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The Role of Innate Lymphoid Cells in the Regulation of Immune Homeostasis in Sepsis-Mediated Lung Inflammation

Cited by 10 publications

References 95 publications

Immune Deregulation in Sepsis and Septic Shock: Reversing Immune Paralysis by Targeting PD-1/PD-L1 Pathway

Immune Deregulation in Sepsis and Septic Shock: Reversing Immune Paralysis by Targeting PD-1/PD-L1 Pathway

Crosstalk between ILC2s and Th2 CD4+ T Cells in Lung Disease

Integrating bulk and single-cell sequencing reveals the phenotype-associated cell subpopulations in sepsis-induced acute lung injury

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