Innate immunity in sarcoidosis pathobiology

  title={Innate immunity in sarcoidosis pathobiology},
  author={Edward S. Chen},
  journal={Current Opinion in Pulmonary Medicine},
  • E. Chen
  • Published 1 September 2016
  • Biology, Medicine
  • Current Opinion in Pulmonary Medicine
Purpose of review The immunopathogenesis of sarcoidosis is considered to involve contributions from both adaptive and innate immune responses. Although the identification of adaptive responses to candidate pathogenic antigens will elucidate mechanisms that regulate inflammation in sarcoidosis, innate mechanisms likely represent the ‘missing link’ to the initiation, maintenance, and resolution of noncaseating granulomatous inflammation, the hallmark feature of sarcoidosis. Furthermore… 

Etiology and Immunopathogenesis of Sarcoidosis: Novel Insights

It is likely that sarcoidosis does not have one single cause but rather is the result of the interplay between different etiologic agents and the immune system in predisposed individuals.

Inflammatory Pathways in Sarcoidosis.

This chapter will outline the current understanding of inflammatory pathways in sarcoidosis which initiate and mediate granulomatous changes or onset of pulmonary fibrosis.

Macrophage polarization in sarcoidosis

This literature review examines the important role of various cytokines and T helper subpopulations in sarcoidosis and pays particular attention to the cells of innate immunity – macrophages in the pathogenesis of this disease.

New concepts in the pathogenesis of sarcoidosis

This review aims to highlight the latest findings, identified from PubMed, EMBASE, and Web of Science, on the pathogenetic mechanisms of sarcoidosis, considering the studies on potential environmental antigens, genetic background and host immune responses.

Sarcoidosis : expression of cell regulatory markers and the influence of patient phenotype on bronchoalveolar lavage cell differential counts

This work found that genetic variants associated with risk of LS and clustered in the extended MHC region were associated with the quantitative levels of BALF macrophages, lymphocytes, and neutrophils, and might help in identifying patients at increased risk of developing more advanced lung disease.

Transcriptome profiles in sarcoidosis and their potential role in disease prediction

All these transcriptomics data confirm the key role of TH1 immune response in sarcoidosis and particularly of interferon-&ggr; (IFN-&GGr;) and type I IFN-driven signaling pathways.

Emerging and potential treatment options for sarcoidosis

Future advances in the care of sarcoidosis will involve therapy of specific problematic phenotypes, treatment of non-granulomatous aspects of the disease, development of pharmacogenetics techniques and biomarkers to personalize care and further focus on quality of life issues endpoints to make treatment decisions.

Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis

Genome-wide BAL transcriptomics identified novel gene expression profiles associated with distinct phenotypic traits in sarcoidosis and is suggestive of the presence of novel molecular and clinical sarcoIDosis endotypes.

Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis

Enrichments in extracellular mtDNA in sarcoidosis are associated with extrapulmonary disease and African American descent and further study into the mechanistic basis of these clinical findings may lead to novel pathophysiologic and therapeutic insights.

Adult-onset systemic autoinflammatory disorders: a clinical approach.

This review aims to describe the most common adult-onset systemic AIDs, focusing mostly on polygenic and mixed-pattern diseases which are expected to be more prevalent in adult patients than monogenic AIDs overall.



Immunology of sarcoidosis.

Serum amyloid A regulates granulomatous inflammation in sarcoidosis through Toll-like receptor-2.

Serum amyloid A is a constituent and innate regulator of granulomatous inflammation in sarcoidosis through Toll-like receptor-2, providing a mechanism for chronic disease and new therapeutic targets.

Dysregulation of p38 and MKP-1 in response to NOD1/TLR4 stimulation in sarcoid bronchoalveolar cells.

The results suggest that enhanced p38 signaling in response to microbial products is caused by abnormal regulation of MKP-1 and contributes to heightened inflammation in sarcoidosis.

M2 polarized macrophages and giant cells contribute to myofibrosis in neuromuscular sarcoidosis.

Cellular Responses to Mycobacterial Antigens Are Present in Bronchoalveolar Lavage Fluid Used in the Diagnosis of Sarcoidosis

Inhibition of immune recognition with monoclonal antibody against Toll-like receptor 2 suggests that induction of innate immunity by mycobacteria contributes to the polarized Th1 immune response.

T Cell Responses to Mycobacterial Catalase-Peroxidase Profile a Pathogenic Antigen in Systemic Sarcoidosis1

Assessment of lung and blood T cell responses to the candidate pathogenic Ag, Mycobacterium tuberculosis catalase-peroxidase in patients with sarcoidosis and patients with or without Löfgren syndrome shows that mKatG specific IFN-γ-expressing blood T cells had similar frequencies, supporting an immunotherapeutic approach to this disease.

Disordered Toll‐like receptor 2 responses in the pathogenesis of pulmonary sarcoidosis

The findings support a potential role for disordered TLR‐2 responses in the pathogenesis of pulmonary sarcoidosis and evaluated the impact of TLR-2 gene deletion in a recently described murine model of T helper type 1 (Th1)‐associated lung disease induced by heat‐killed Propionibacterium acnes.

Toll-like receptor 2 (TLR2) gene polymorphisms are not associated with sarcoidosis in the Japanese population

The results suggest that TLR2 polymorphisms are not significantly related to the pathogenesis of sarcoidosis in the Japanese population.

Mycobacterial catalase–peroxidase is a tissue antigen and target of the adaptive immune response in systemic sarcoidosis

A limited proteomics approach was used to detect tissue antigens that were poorly soluble in neutral detergent and resistant to protease digestion, consistent with the known biochemical properties of granuloma-inducing sarcoidosis tissue extracts, and Matrix-assisted laser desorption/ionization time of flight mass spectrometry identified Mycobacterium tuberculosis catalase–peroxidase (mKatG) as one of these tissue antIGens.

Plasma chitotriosidase and CCL18 as surrogate markers for granulomatous macrophages in sarcoidosis.