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Disease: mechanism | sp. | Biomarker studied | Reference |
|
Asthma |
T-reg cells from patients with allergic asthma have lower expression of FoxP3, XCL1 and XCR1, leading to suboptimal inhibitory function. Also, impaired chemotactic response to CCL1 correlates with asthma severity. | H | FoxP3 | [79, 81, 122] |
XCL1 |
XCR1 |
CCL1 |
Increased bronchial density of T-regs, effector T cells, proliferative T cells and activated CD8+ T cells in asthmatics exposed to occupational noxious stimulus shows that both the effector T cells and the inhibitory T-reg, system are activated in asthma. | H | CD4+ | [83] |
CD8+ |
Airway hyper-reactiveness is modulated by regulatory T cells through induction of TGF-β. Regulatory T cells, modulate lung eosinophilia and Th2 response in allergen-induced airway inflammation. | M | TGF-β | [77, 123] |
IL-5 |
IL-13 |
Drugs targeting IL-5 decrease asthma exacerbation rate by up to 50% in patients with eosinophilic phenotype. | H | IL-5 | [124] |
|
COPD |
During COPD exacerbations, increased proportions of pro-inflammatory T-reg subpopulations and decreased proportion of suppressive T-regs are observed. Higher Th17 cell counts are also observed, decreasing the T-regs/Th17 ratio. Elevated regulatory T-cells are observed in pulmonary lymphoid follicles. | H | IL-17 | [55, 64–66] |
IFN-γ |
TGF-β |
IL-10 |
CD62L |
FoxP3+ |
Regulatory T cells are present in lower counts in the small airways of patients with COPD as compared to healthy controls. | H | IL-10 | [56] |
IL-17 |
TGF-β |
Caveolin-1 plays a crucial role in the imbalance between Th17 and T-regs. Populations in patients with COPD. | H | Cav-1 | [62] |
TGF-β |
IL-17 |
Peripheral blood T-regs from COPD have an impaired function to suppress CD4+ T-cell activation when stimulated in vitro. | H | Foxp3− CD4+ | [60] |
CD45RO+ |
Proportion of circulating T-regs in COPD patients decreased significantly following long-term treatment with bronchodilators and inhaled steroids. | H | IL-17A | [67] |
IL-8 |
TNF-α |
IL-10 |
|
IPF |
Higher expression of Semaphorin 7a is observed on regulatory T cells from individuals with IPF. | H/M | SEMA7A | [117] |
TGF-β1 |
IFN-γ |
IL-4 |
IL-10 |
IL-17A |
Individuals with IPF have lower proportions of regulatory T cells in bronchoalveolar lavage and peripheral blood and these have limited inhibitory activity. Low T-reg cell counts are inversely correlated with disease severity. | H | TNF-α | [108, 112] |
IFN-γ |
Ki-67 | |
|
Lung cancer |
Higher proportions of circulating regulatory T-cells are present on lung cancer patients. These are associated to worse clinical outcome. | H | IL-10 | [98, 125] |
|
TGF-β |
IFN-γ |
Tumor production of PGE2 via COX-2 induces regulatory T cell activity by increasing expression of FoxP3. A positive correlation exists between the degree of Treg infiltration and COX-2 expression in NSCLC tumor samples. Recurrence free survival decreases with higher COX-2 expression. | M / H | COX-2 & PGE2 | [126, 127] |
| EP2 & 4 R |
| FoxP3 |
|
Sarcoidosis |
Higher counts of Th17 lymphocytes and lower counts of T-reg. Cells are observed in peripheral blood samples of patients with sarcoidosis. | H | ROR-γt | [42] |
Circulating regulatory T cell counts are increased in sarcoidosis patients, however these have inefficient suppressive ability. Levels are reduced significantly following corticosteroid therapy. | H | IL-2 | [43, 128] |
IL-17A |
TGF-β1 |
IL-6 |
IFN-γ |
IL-10 |
CCL20 |
A higher ratio of T-helper to T-suppressor cells are observed in the airways of patients with sarcoidosis. These imbalances lead to granuloma formation. Bronchial T-regs in active sarcoidosis highly express ICOS. | H | ICOS ICOS-L | [38, 39] |
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