The lungs at the frontlines of immunity

doi:10.1038/ni.3069

Cited by 16 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As IFN-γ secreted by activated T lymphocytes is the main inducer of PD-L1 5 , 24 , and thus responsible for adaptive PD-L1-mediated immune resistance 9 , 10 , we were interested in elucidating body-wide changes in ligand expression in response to this important cytokine. Interestingly, the lung turned out to be the organ with the strongest specific PD-L1 upregulation, which teleologically appears meaningful since the lung is a vital organ that is continuously exposed to a high level of antigens that can potentially induce IFN-γ-secreting lymphocytes 35 , 43 , 44 . In contrast, BAT is not continuously exposed to microorganisms.…”

Section: Discussionmentioning

confidence: 93%

“…Moreover, we found particularly pronounced PD-L1 induction in the lung in response to its major inducer IFN-γ 5 , 24 . Subsequent FACS analyses assigned the highest increase to non-hematopoietic cells, suggesting that the lung, which is a vital organ continuously exposed to a variety of antigens 35 , is strongly protected against immune attacks by PD-L1 upregulation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

High-Resolution PET Imaging with Therapeutic Antibody-based PD-1/PD-L1 Checkpoint Tracers

et al. 2016

View full text Add to dashboard Cite

Checkpoint-blocking antibodies like those targeting the PD-1/PD-L1 pathway have revolutionized oncology. We developed radiotracers based on therapeutic checkpoint-blocking antibodies permitting sensitive and high-resolution PET imaging of both PD-1 and PD-L1 in immunocompetent mice. ImmunoPET of naive mice revealed similar overall expression patterns for PD-1 and PD-L1 in secondary lymphoid organs (spleen and lymph nodes). Interestingly, PD-L1 was also detected in brown adipose tissue (BAT), confirming the notion that BAT is immunologically relevant. Under pathophysiological conditions, strong expression of the receptor/ligand pair was also found in non-lymphoid tissues. Both were specifically detected in malignant tumors. PD-1 was readily detected after combined immunoradiotherapy causing massive tumor infiltration by PD-1+ lymphocytes. PD-L1 tracer uptake was reduced in PD-L1 knockout tumors. Moreover, monitoring the expression changes of PD-L1 in response to its main inducer, the effector T cell cytokine IFN-γ, revealed robust upregulation in the lung. This suggests that T cell responses in the lung, a vital organ continuously exposed to a variety of antigens, are strongly restrained by the PD-1 checkpoint. In turn, this could explain the association of PD-1 checkpoint inhibition with potentially fatal immune-mediated pneumonitis and partially also its efficacy in lung cancer.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

High-Resolution PET Imaging with Therapeutic Antibody-based PD-1/PD-L1 Checkpoint Tracers

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Mucosal immune tolerance mechanisms are most prominently studied between the immune cells of the intestinal lining and commensal microbiota ( 1 , 2 ). However, immune tolerance is also of great importance in other mucosal tissues, such as the lung, where the role of commensal microbiota is not well characterized ( 3 , 4 ). Recently, it has become better appreciated that mechanisms of immune tolerance may be shared across various organs, especially between the mucosal tissues where similar resident cell types sample and surveil antigens at the external borders ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

Dendritic cell expression of the signaling molecule TRAF6 is required for immune tolerance in the lung

Han

Walsh

Kim

et al. 2017

International Immunology

View full text Add to dashboard Cite

show abstract

“…It is crucial to understand that treating lung injury frequently requires treating the inflammation (e.g., infections, physical trauma). Given that immune cells constitute a typical component of the human lungs’ normal structure and operation, this problem may be particularly relevant to inflammatory illnesses of the respiratory system ( 236 ). Consequently, there is a critical need for stratified medicine based on genomes, biomarkers, and also inflammatory profiles to identify IPF patients who may benefit from combining standard-of-care “anti-fibrotic” medication with co-treatment with anti-inflammatory/immunomodulatory therapy.…”

Section: Idiopathic Lung Diseasesmentioning

confidence: 99%

Immune-mediated lung diseases: A narrative review

Sweis

Alnaimat

et al. 2023

Front. Med.

View full text Add to dashboard Cite

The role of immunity in the pathogenesis of various pulmonary diseases, particularly interstitial lung diseases (ILDs), is being increasingly appreciated as mechanistic discoveries advance our knowledge in the field. Immune-mediated lung diseases demonstrate clinical and immunological heterogeneity and can be etiologically categorized into connective tissue disease (CTD)-associated, exposure-related, idiopathic, and other miscellaneous lung diseases including sarcoidosis, and post-lung transplant ILD. The immunopathogenesis of many of these diseases remains poorly defined and possibly involves either immune dysregulation, abnormal healing, chronic inflammation, or a combination of these, often in a background of genetic susceptibility. The heterogeneity and complex immunopathogenesis of ILDs complicate management, and thus a collaborative treatment team should work toward an individualized approach to address the unique needs of each patient. Current management of immune-mediated lung diseases is challenging; the choice of therapy is etiology-driven and includes corticosteroids, immunomodulatory drugs such as methotrexate, cyclophosphamide and mycophenolate mofetil, rituximab, or other measures such as discontinuation or avoidance of the inciting agent in exposure-related ILDs. Antifibrotic therapy is approved for some of the ILDs (e.g., idiopathic pulmonary fibrosis) and is being investigated for many others and has shown promising preliminary results. A dire need for advances in the management of immune-mediated lung disease persists in the absence of standardized management guidelines.

show abstract

The lungs at the frontlines of immunity

Cited by 16 publications

References 0 publications

High-Resolution PET Imaging with Therapeutic Antibody-based PD-1/PD-L1 Checkpoint Tracers

High-Resolution PET Imaging with Therapeutic Antibody-based PD-1/PD-L1 Checkpoint Tracers

Dendritic cell expression of the signaling molecule TRAF6 is required for immune tolerance in the lung

Immune-mediated lung diseases: A narrative review

Contact Info

Product

Resources

About