Researchers have discovered that patients with pulmonary sarcoidosis have an imbalance in two subsets of immune cells, namely B-cells and follicular T-helper cells — findings that support the potential role of autoimmune mechanisms in sarcoidosis development.
The study, “Imbalance in B cell and T Follicular Helper Cell Subsets in Pulmonary Sarcoidosis,”was published in the journal Nature Scientific Reports.
Sarcoidosis is an inflammatory disease characterized by the abnormal buildup, in tissues and organs, of clumps of immune cells known as granulomas. Although the cause of the disease remains unclear, immune cells called B-cells and follicular T-helper cells (Tfh) have been identified as important contributors.
B-cells are a type of immune cell that produces antibodies once activated. Different types of B-cells can be identified by the expression of different markers on the cell’s surface.
Naive B-cells have not yet been exposed to antigens (protein markers that allow cells to be identified as “self” or “non-self” by the immune system). Once they are exposed, they become either a memory B-cell or a plasma cell, and start producing specific antibodies. Plasma cells live for a relatively short time, while memory B-cells last for a long time.
T-cells are also vital immune cells, activating other immune cells to strengthen the immune response. Tfh cells are critical for the production of plasma and memory B-cells, and regulate all stages of B-cell differentiation and activation occurring in peripheral tissues. Different types of Tfh cells have distinct capacities to regulate B-cells.
Previous research has suggested that sarcoidosis patients have altered B-cells compared to healthy people. Moreover, treatment with anti-B-cell therapies was found to lead to improvements in sarcoidosis patients, which suggests that B-cells may play a role in the disease. The imbalanced B-cell subsets may be due to an imbalance in Tfh cells, but the role of Tfh cells in sarcoidosis is unclear.
Therefore, a team led by researchers at St. Petersburg State University, in Russia, investigated the involvement of peripheral blood B-cells and Tfh cells in pulmonary sarcoidosis.
The researchers analyzed the levels of B-cells and Tfh cells in blood samples from 37 patients with pulmonary sarcoidosis, and 35 age- and sex-matched healthy controls.
The analysis revealed that sarcoidosis patients had significantly more B-cells in their blood (14.48%) compared to healthy controls (11.09%). Further analysis showed that within the subset of B-cells, pulmonary sarcoidosis patients had fewer memory B-cells, and a significantly more “naive” and activated B-cells.
Specific types of B-cells have different regulatory abilities, including the production of high levels of IL-10, an anti-inflammatory molecule. The levels of two of these B-cell types were found to be significantly higher in patients than in healthy controls. The levels registered for CD24+++ CD38++ B-cells were 9.82% in sarcoidosis patients, compared with 4.69% in healthy controls; and for CD5 + CD27− cells, the levels were 17.41% in patients versus 8.21% in healthy controls.
“These findings indicate that at least two B-cell subsets — CD24+++ CD38+++ and CD5 + CD27−, that according to the literary data were enriched with IL-10-producing cells — are strongly increased in sarcoidosis patients,” the researchers wrote.
Next, they measured the levels of Tfh cells. Sarcoidosis patients showed a significantly higher proportion (39.7%) of a specific type of Tfh cells, known as CXCR5-expressing central memory cells, compared to healthy controls (32.3%). This suggests that the expansion of this memory Tfh cell subset occurs during sarcoidosis.
The levels of different types of Tfh cells were then assessed by looking at the expression levels of three chemokine receptors (CCR6, CXCR3, and CCR4). Chemokine receptors trigger an immune response upon binding of a signaling molecule (chemokine).
Results showed that sarcoidosis patients had significantly higher levels of Tfh cells expressing CCR4, including a type of Tfh cell known as Tfh2, considered to have a pro-inflammatory role. However, no significant differences were seen in Tfh cells lacking expression of all chemokine receptors, or classical Tfh17 cells (which are also thought to have a pro-inflammatory role).
In contrast, the levels of Tfh1 cells and Tfh17.1 cells were significantly decreased in sarcoidosis patients compared to healthy controls. Tfh1 cells are thought to have a regulatory role, and can induce the death of “naive” activated B-cells.
Overall, “these data point to a potential involvement of B-cells in the pathogenesis of sarcoidosis,” the researchers wrote. “This is the first study to demonstrate the association of circulating imbalance Tfh cells … in the development of sarcoidosis.”
The results can be considered as new evidence of the autoimmune mechanisms in sarcoidosis development, the researchers added, which may lead to new directions for future clinical studies and treatment strategies.
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