Deficiency and altered phenotype of mucosal-associated invariant T cells in systemic sclerosis.
J Scleroderma Relat Disord
; 9(1): 67-78, 2024 Feb.
Article
en En
| MEDLINE
| ID: mdl-38333523
ABSTRACT
Objective:
Systemic sclerosis is an autoimmune disease characterized by fibrosis of the skin and internal organs including the lung. Mucosal-associated invariant T cells are innate-like T lymphocytes able to produce various cytokines and cytotoxic mediators such as granzyme B. A large body of evidence supports a role of mucosal-associated invariant T cells in autoimmune disease but more recent reports suggest also a potential role in fibrotic conditions. Therefore, we herein addressed the question as whether mucosal-associated invariant T cells may have an altered profile in systemic sclerosis.Methods:
Mucosal-associated invariant T cell frequency was analyzed by flow cytometry, using fresh peripheral blood from 74 consecutive systemic sclerosis patients who were compared to 44 healthy donors. In addition, in-depth mucosal-associated invariant T cell phenotype and function were analyzed in unselected 29 women with systemic sclerosis who were compared to 23 healthy women donors.Results:
Proportion of circulating mucosal-associated invariant T cells was significantly reduced by 68% in systemic sclerosis compared to healthy donors (0.78% in systemic sclerosis vs 2.5%, p < 0.0001). Within systemic sclerosis subsets, mucosal-associated invariant T cells were reduced in patients with interstitial lung disease (systemic sclerosis-interstitial lung disease) (0.56% vs 0.96% in patients without interstitial lung disease, p = 0.04). Moreover, in systemic sclerosis patients, mucosal-associated invariant T cells displayed an activated phenotype indicated by markedly increased CD69+ mucosal-associated invariant T cell frequency (20% mucosal-associated invariant T cell CD69+ compared to 9.4% in healthy donors, p = 0.0014). Interestingly, mucosal-associated invariant T cells from systemic sclerosis-interstitial lung disease patients had a more pronounced altered phenotype compared to systemic sclerosis without interstitial lung disease with a correlation between mucosal-associated invariant T cells expressing CCR6+ and mucosal-associated invariant T cell frequency (r = 0.8, p = 0.006).Conclusion:
Circulating mucosal-associated invariant T cells were reduced and exhibited an activated phenotype in systemic sclerosis patients. This peripheral mucosal-associated invariant T cell deficiency may be related to enhanced apoptosis and/or homing in inflamed tissue, particularly in systemic sclerosis-interstitial lung disease patients.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Revista:
J Scleroderma Relat Disord
Año:
2024
Tipo del documento:
Article
País de afiliación:
Francia