PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity

Helou, Doumet Georges; Shafiei-Jahani, Pedram; Lo, Richard; Howard, Emily; Hurrell, Benjamin P.; Galle-Treger, Lauriane; Painter, Jacob D.; Lewis, Gavin; Soroosh, Pejman; Sharpe, Arlene H.; Akbari, Omid

doi:10.1038/s41467-020-17813-1

Cited by 108 publications

(107 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therapeutic blockade of PD-1 in these animals partially restored ILC2 functions and ameliorated the metabolic homeostasis [141]. In line with these findings, Helou et al [142] reported that PD-1 is inducible on pulmonary ILC2s upon intranasal IL-33 stimulation. By comparing the transcriptomic profiles of pulmonary ILC2s from WT and PD-1 knockout mice the authors highlight an in cis interaction between PD-1 and PD-L1 in IL-33 activated ILC2s.…”

Section: Pd-1supporting

confidence: 56%

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Pesce¹,

Trabanelli

Vito

et al. 2020

Cancers

View full text Add to dashboard Cite

Immune checkpoints refer to a plethora of inhibitory pathways of the immune system that play a crucial role in maintaining self-tolerance and in tuning the duration and amplitude of physiological immune responses to minimize collateral tissue damages. The breakdown of this delicate balance leads to pathological conditions, including cancer. Indeed, tumor cells can develop multiple mechanisms to escape from immune system defense, including the activation of immune checkpoint pathways. The development of monoclonal antibodies, targeting inhibitory immune checkpoints, has provided an immense breakthrough in cancer therapy. Immune checkpoint inhibitors (ICI), initially developed to reverse functional exhaustion in T cells, recently emerged as important actors in natural killer (NK)-cell-based immunotherapy. Moreover, the discovery that also helper innate lymphoid cells (ILCs) express inhibitory immune checkpoints, suggests that these molecules might be targeted on ILCs, to modulate their functions in the tumor microenvironment. Recently, other strategies to achieve immune checkpoint blockade have been developed, including miRNA exploiting systems. Herein, we provide an overview of the current knowledge on inhibitory immune checkpoints on NK cells and ILCs and we discuss how to target these innate lymphocytes by ICI in both solid tumors and hematological malignancies.

show abstract

Section: Pd-1supporting

confidence: 56%

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Pesce¹,

Trabanelli

Vito

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…The following human antibodies were used: FITC- Lineage that includes mixture of CD3, CD14, CD16, CD19, CD20, CD56 (348801; 1/100), FITC-CD235a (HI264; 1/500), FITC-FCeRIa (AER-37; 1/100), FITC-CD1a (HI149;1/100), FITC-CD123 (6H6; 1/100), FITC-CD5 (L17F12; 1/100), APCCy7-CD45 (HI30; 1/100), PE-CD294 (CRTH2) (BM16; 1/100), PE/Cy7-CD127 (A019D5; 1/100), and BV421 anti-CD200R (OX-108; 1/200) were purchased from BioLegend. Purified human ILC2s were cultured with rhIL-2 (20 ng/mL) and rhIL-7 (20 ng/mL) and adoptively transferred to Rag2 −/− Il2rg −/− mice (5 × 10 4 cells per mouse) 43 .…”

Section: Methodsmentioning

confidence: 99%

CD200–CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma

et al. 2021

Self Cite

View full text Add to dashboard Cite

The prevalence of asthma and airway hyperreactivity (AHR) is increasing at an alarming rate. Group 2 innate lymphoid cells (ILC2s) are copious producers of type 2 cytokines, which leads to AHR and lung inflammation. Here, we show that mouse ILC2s express CD200 receptor (CD200R) and this expression is inducible. CD200R engagement inhibits activation, proliferation and type 2 cytokine production, indicating an immunoregulatory function for the CD200–CD200R axis on ILC2s. Furthermore, CD200R engagement inhibits both canonical and non-canonical NF-κB signaling pathways in activated ILC2s. Additionally, we demonstrate both preventative and therapeutic approaches utilizing CD200R engagement on ILC2s, which lead to improved airway resistance, dynamic compliance and eosinophilia. These results show CD200R is expressed on human ILC2s, and its engagement ameliorates AHR in humanized mouse models, emphasizing the translational applications for treatment of ILC2-related diseases such as allergic asthma.

show abstract

“…Interleukin (IL)-4, IL-5, IL-9 and IL-13 are important cytokines that play key roles in type 2 immunity, and are usually involved in allergic diseases or during helminthic parasitic infections ( 8 , 9 ). Th2 cells and certain myeloid cells are considered the primary source of these type 2 cytokines ( 10 , 11 ); however, recent studies have reported that a rare subpopulation of innate lymphocytes are the predominant source ( 12 – 14 ). Type 2 innate lymphoid cells (ILC2s), which were first discovered as non-T and B cells ( 15 , 16 ), play a defensive role in the initial stage of helminthic infestation ( 17 ), and are considered a major component of type 2 immunity in lungs ( 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review)

Zhu

Lü

2021

Mol Med Rep

View full text Add to dashboard Cite

Type 2 innate lymphoid cells (ILC2s) are important innate immune cells that are involved in type 2 inflammation, in both mice and humans. ILC2s are stimulated by factors, including interleukin (IL)-33 and IL-25, and activated ILC2s secrete several cytokines that mediate type 2 immunity by inducing profound changes in physiology, including activation of alternative (M2) macrophages. M2 macrophages possess immune modulatory, phagocytic, tissue repair and remodeling properties, and can regulate ILC2s under infection. The present review summarizes the role of ILC2s as innate cells and M2 macrophages as anti-inflammatory cells, and discusses current literature on their important biological significance. The present review also highlights how the crosstalk between ILC2s and M2 macrophages contributes to lung development, induces pulmonary parasitic expulsion, exacerbates pulmonary viral and fungal infections and allergic airway diseases, and promotes the development of lung diseases, such as pulmonary fibrosis, chronic obstructive pulmonary disease and carcinoma of the lungs. Contents

show abstract

PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity

Cited by 108 publications

References 58 publications

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

CD200–CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma

A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review)

Contact Info

Product

Resources

About