Updates on T helper type 17 immunity in respiratory disease

Iwanaga, Naoki; Kolls, Jay K.

doi:10.1111/imm.13006

Cited by 56 publications

(53 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mtb-specific IL-17+ cells peaked at week 7 and were detected mainly in BAL, being largely absent in blood. The accumulation of IL-17 cytokine-producing CD4 T cells in lung compartments is consistent with the known preferential accumulation of Th 17 cells at mucosal sites during infection(49). Various studies in mice have also suggested that Th 17 cells play an important role in protective immunity against TB, both in the context of vaccination (50) as well as in the context of disease progression (51, 52).…”

Section: Discussionsupporting

confidence: 81%

Control of Mycobacterium tuberculosis Infection in Lungs is Associated with Recruitment of Antigen-Specific Th1 and Th17 cells Co-expressing CXCR3 and CCR6

Shanmugasundaram

Bucşan

Ganatra

et al. 2020

Preprint

View full text Add to dashboard Cite

27Mycobacterium tuberculosis (Mtb)-specific T cell responses associated with immune control 28 during asymptomatic latent tuberculosis infection (LTBI) remain poorly understood. Using a non-29 human primate (NHP) aerosol model, we studied the kinetics, phenotypes and functions of Mtb 30 antigen-specific T cells in peripheral and lung compartments of Mtb-infected asymptomatic 31 rhesus macaques by longitudinally sampling blood and bronchoalveolar lavage (BAL), for up to 32 24 weeks post-infection. We found significantly higher frequencies of Mtb-specific effector and 33 memory CD4 and CD8 T cells producing IFN-γ in the airways compared to peripheral blood, 34 which were maintained throughout the study period. Moreover, Mtb-specific IL-17+ and IL-35 17/IFN-γ double-positive T cells were present in the airways but were largely absent in the 36 periphery, suggesting that balanced mucosal Th 1 /Th 17 responses are associated with LTBI. The 37 majority of Mtb-specific CD4 T cells that homed to the airways expressed the chemokine 38 receptor CXCR3 and co-expressed CCR6. Notably, CXCR3+CD4+ cells were found in 39 granulomatous and non-granulomatous regions of the lung and inversely correlated with Mtb 40 burden. Our findings provide novel insights into antigen-specific T cell responses associated 41 with asymptomatic Mtb infection that are relevant for developing better strategies to control TB. 42 43 46 51 (LTBI)(1). Individuals with LTBI are defined as having a positive tuberculin skin test (TST) 52 and/or Interferon-gamma Release Assay (IGRA), a normal chest radiograph and the absence of 53 clinical signs and symptoms of disease(2). Latently-infected individuals are generally thought to 54 contain Mtb within granulomatous lesions in the lung without completely eradicating bacteria, 55 although direct evidence for the persistence of Mtb in human LTBI is lacking. Moreover, it is 56 increasingly recognized that clinically asymptomatic individuals likely reflect a spectrum of 57 infection outcomes, ranging from individuals who may have eliminated infection, to those with 58 low levels of replicating or non-replicating persistent bacteria, to individuals who may harbor 59 actively replicating bacteria without exhibiting overt clinical symptoms(3-5). Identifying immune 60 responses associated with asymptomatic Mtb infection states will provide key insights into 61 mechanisms of immune control that protect against progressing to active TB disease. 62 63 Antigen-specific T cell responses are critical for immune control of Mtb infection. In response to 64 Mtb infection, the majority of infected people mount robust CD4 T cell responses involving T 65 helper 1 (Th 1 ) cytokines such as IFN-γ and TNF-α, which are important for activating 66 macrophages and curtailing Mtb replication in the lung(6, 7). In addition, IL-17 and Th 17 67 responses have emerged as important for protective immunity against TB, but mucosal Mtb-68 specific Th 17 responses during immune control of LTBI in humans remain poorly studied. In 69 general, the na...

show abstract

Section: Discussionsupporting

confidence: 81%

Control of Mycobacterium tuberculosis Infection in Lungs is Associated with Recruitment of Antigen-Specific Th1 and Th17 cells Co-expressing CXCR3 and CCR6

Shanmugasundaram

Bucşan

Ganatra

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The relation between Th17 cells and fibrosis has been investigated in recent years. Th17 cells serve as a key component in mucosal immunity including the respiratory tract ( 98 ). In a hypersensitivity pneumonitis mouse model established by repeated exposure to Saccharopolyspora rectivirgula , increased Th17 were responsible for the inflammatory and fibrotic responses ( 36 ).…”

Section: The Role and Mechanisms Of T Cells In Fibrosis And Fibrotic mentioning

confidence: 99%

T Cells in Fibrosis and Fibrotic Diseases

2020

View full text Add to dashboard Cite

Fibrosis is the extensive deposition of fibrous connective tissue, and it is characterized by the accumulation of collagen and other extracellular matrix (ECM) components. Fibrosis is essential for wound healing and tissue repair in response to a variety of triggers, which include infection, inflammation, autoimmune disorder, degenerative disease, tumor, and injury. Fibrotic remodeling in various diseases, such as liver cirrhosis, pulmonary fibrosis, renal interstitial fibrosis, myocardial infarction, systemic sclerosis (SSc), and graft-versus-host disease (GVHD), can impair organ function, causing high morbidity and mortality. Both innate and adaptive immunity are involved in fibrogenesis. Although the roles of macrophages in fibrogenesis have been studied for many years, the underlying mechanisms concerning the manner in which T cells regulate fibrosis are not completely understood. The T cell receptor (TCR) engages the antigen and shapes the repertoire of antigen-specific T cells. Based on the divergent expression of surface molecules and cell functions, T cells are subdivided into natural killer T (NKT) cells, γδ T cells, CD8 + cytotoxic T lymphocytes (CTL), regulatory T (Treg) cells, T follicular regulatory (Tfr) cells, and T helper cells, including Th1, Th2, Th9, Th17, Th22, and T follicular helper (Tfh) cells. In this review, we summarize the pro-fibrotic or anti-fibrotic roles and distinct mechanisms of different T cell subsets. On reviewing the literature, we conclude that the T cell regulations are commonly disease-specific and tissue-specific. Finally, we provide perspectives on microbiota, viral infection, and metabolism, and discuss the current advancements of technologies for identifying novel targets and developing immunotherapies for intervention in fibrosis and fibrotic diseases.

show abstract

“…Interleukin (IL)-17 is an important cytokine for regulating immune homeostasis, and the aberrant expression of IL-17 has been suggested to contribute to a number of pathologies, including asthma, pneumonitis and the generation or exacerbation of pulmonary fibrosis (20). IL-35, a recently identified heterodimeric cytokine, has been implicated to serve a crucial role in several immune-associated diseases, such as autoimmune diseases and viral infections, as well as in tumors (21).…”

Section: Elevated Levels Of Il-17a and Il-35 In Plasma And Bronchoalvmentioning

confidence: 99%

Elevated levels of IL‑17A and IL‑35 in plasma and bronchoalveolar lavage fluid are associated with checkpoint inhibitor pneumonitis in patients with non‑small cell lung cancer

Wang

Lou

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

Advances in the immunology have identified that interleukin (IL)-17 and IL-35 are cytokines with diverse functions, serving important roles in autoimmune diseases and chronic inflammation. Checkpoint inhibitor pneumonitis (CIP) is focal or diffuse lung inflammation induced by immune checkpoint inhibitors and the underlying pathogenesis has not been fully explored. The aim of the present study was to investigate the roles of IL-17A and IL-35, and the correlation between their levels and different T cell subsets in CIP. The levels of IL-17A and IL-35 in peripheral blood and bronchoalveolar lavage fluid (BALF) were measured in patients with non-small cell lung cancer (NSCLC) with CIP, and the corresponding controls. The percentages of helper T lymphocyte (Th)1, Th2 and Th17 cells, and regulatory T cells (Tregs) in the peripheral blood were synchronically detected. Serum levels of IL-17A and IL-35 were significantly increased at the time of CIP diagnosis compared with the baseline, and significantly decreased upon clinical recovery or improvement. IL-17A and IL-35 were also increased in the BALF during the development of CIP compared with the baseline. Serum levels of IL-17A were positively correlated with the percentages of Th1 and Th17 cells as well as the ratio of Th17 to Tregs, but negatively associated with the frequency of Tregs in CIP. Serum levels of IL-35 were positively correlated with the percentages of Th1 and Tregs, and with the ratio of Th1 to Th2 cells in CIP. A higher frequency of Th1 and Th17 cells, as well as higher ratios of Th17 to Tregs and Th1 to Th2 cells were detected upon development of CIP comparing with the baseline. These data suggested that the activation of Th1 and Th17 cells, as well as Treg inhibition contributed to the imbalanced ratios of Th1 to Th2 and Th17 to Tregs, which resulted in increased secretion of IL-17A and IL-35 in the plasma and BALF; this may present a valuable index to monitor the development and severity of CIP in patients with NSCLC receiving immunotherapy.

show abstract

Updates on T helper type 17 immunity in respiratory disease

Cited by 56 publications

References 77 publications

Control of Mycobacterium tuberculosis Infection in Lungs is Associated with Recruitment of Antigen-Specific Th1 and Th17 cells Co-expressing CXCR3 and CCR6

Control of Mycobacterium tuberculosis Infection in Lungs is Associated with Recruitment of Antigen-Specific Th1 and Th17 cells Co-expressing CXCR3 and CCR6

T Cells in Fibrosis and Fibrotic Diseases

Elevated levels of IL‑17A and IL‑35 in plasma and bronchoalveolar lavage fluid are associated with checkpoint inhibitor pneumonitis in patients with non‑small cell lung cancer

Contact Info

Product

Resources

About