The immune paradox of sarcoidosis and regulatory T cells

Miyara, Makoto; Amoura, Zahir; Parizot, Christophe; Badoual, Cécile; Dorgham, Karim; Trad, S.; Kambouchner, Marianne; Valeyre, Dominique; Chapelon-Abric, C.; Debré, Patrice; Piette, Jean‐Charles; Gorochov, Guy

doi:10.1084/jem.20050648

Cited by 383 publications

(331 citation statements)

References 54 publications

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“…Number of subject's data included for years ϭ 10, 20, 30, 40 years from first exposure displayed. (37). In additional support of this hypothesis is our finding that the presence of even one copy of the alternate haplotype containing the Ϫ509T and codon 10C results in a lack of progression of FEV 1 , FVC, TLC, and PaO 2 at rest or maximum exercise over time in CBD and in a lower risk of having Scadding stage II, III, or IV chest radiograph in sarcoidosis.…”

Section: Discussionsupporting

confidence: 70%

TGF-β1 Variants in Chronic Beryllium Disease and Sarcoidosis

Jonth

Silveira

Fingerlin³

et al. 2007

The Journal of Immunology

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Evidence suggests a genetic predisposition to chronic beryllium disease (CBD) and sarcoidosis, which are clinically and pathologically similar granulomatous lung diseases. TGF-β1, a cytokine involved in mediating the fibrotic/Th1 response, has several genetic variants which might predispose individuals to these lung diseases. We examined whether certain TGF-β1 variants and haplotypes are found at higher rates in CBD and sarcoidosis cases compared with controls and are associated with disease severity indicators for both diseases. Using DNA from sarcoidosis cases/controls from A Case Control Etiologic Study of Sarcoidosis Group (ACCESS) and CBD cases/controls, TGF-β1 variants were analyzed by sequence-specific primer PCR. No significant differences were found between cases and controls for either disease in the TGF-β1 variants or haplotypes. The −509C and codon 10T were significantly associated with disease severity indicators in both CBD and sarcoidosis. Haplotypes that included the −509C and codon 10T were also associated with more severe disease, whereas one or more copies of the haplotype containing the −509T and codon 10C was protective against severe disease for both sarcoidosis and CBD. These studies suggest that the −509C and codon 10T, implicated in lower levels of TGF-β1 protein production, are shared susceptibility factors associated with more severe granulomatous disease in sarcoidosis and CBD. This association may be due to lack of down-regulation by TGF-β1, although future studies will be needed to correlate TGF-β1 protein levels with known TGF-β1 genotypes and assess whether there is a shared mechanisms for TGF-β1 in these two granulomatous diseases.

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Section: Discussionsupporting

confidence: 70%

TGF-β1 Variants in Chronic Beryllium Disease and Sarcoidosis

Jonth

Silveira

Fingerlin³

et al. 2007

The Journal of Immunology

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“…Natural Treg cells are Foxp3 ϩ and belong to the CD4 ϩ CD25 high T cells subpopulation with marked suppressive capacity (32,33). Consistently with their natural Treg cell phenotype, expanded CD4 ؉ CD25 ؉ T cells but not the expanded CD4 ؉ CD25 Ϫ T cells from PCM patients suppressed PHA-induced allogeneic T cell proliferation ( Figs.…”

Section: Discussionmentioning

confidence: 55%

Systemic and Local Characterization of Regulatory T Cells in a Chronic Fungal Infection in Humans

Cavassani¹,

Campanelli²,

Moreira³

et al. 2006

The Journal of Immunology

128

105

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The long-term persistence of pathogens in a host is a hallmark of certain infectious diseases, including schistosomiasis, leishmaniasis, and paracoccidioidomycosis (PCM). Natural regulatory T (Treg) cells are involved in control of the immune responses, including response to pathogens. Because CTLA-4 is constitutively expressed in Treg cells and it acts as a negative regulator of T cell activation in patients with PCM, here we investigated the involvement of Treg cells in the control of systemic and local immune response in patients with PCM. We found that the leukocyte subsets were similar in patients and controls, except for CD11c+CD1a+ cells. However, a higher frequency of CD4+CD25+ T cells expressing CTLA-4, glucorticoid-inducible TNFR, membrane-bound TGF-β, and forkhead-box 3 were observed in PBMC of patients. In accordance, these cells exhibited stronger suppressive activity when compared with those from controls (94.0 vs 67.5% of inhibition of allogeneic T cell proliferation). In addition, the data showed that CD4+CD25+ T cells expressing CTLA-4+, glucocorticoid-inducible TNFR positive, CD103+, CD45RO+, membrane-bound TGF-β, forkhead-box 3 positive, and the chemokines receptors CCR4 and CCR5 accumulate in the Paracoccidioides brasiliensis-induced lesions. Indeed, the secreted CCL17 and CCL22, both associated with the migration of Treg cells to peripheral tissues, were also detected in the biopsies. Moreover, the CD4+CD25+ T cell derived from lesions, most of them TGF-β+, also exhibited functional activity in vitro. Altogether, these data provide the first evidence that Treg cells play a role in controlling local and systemic immune response in patients with a fungal-induced granulomatous disease advancing our understanding about the immune regulation in human chronic diseases.

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“…Patients with overproduction of calcitriol due to uncontrolled extrarenal CYP1a expression, e.g., sarcoidosis patients [31][32][33][34], suffer from peripheral immunological anergy and show enhanced numbers of Treg cells [35]. In vitro, calcitriol-stimulated dendritic cells can promote the development of Treg cells [10] and calcitriol directly enhances expression of IL-10 by Th cells [11].…”

Section: Discussionmentioning

confidence: 99%