Illustration of immune cell balance in SLE

SLE and Immune Imbalance: How Th17/SIGIRR Ratios Could Change Everything

Lena Voss in Health & Wellness December 2025 • 4 min read.

"New research highlights the critical role of immune cell ratios in Systemic Lupus Erythematosus, offering hope for targeted therapies."

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a breakdown in self-tolerance, leading to immune complexes depositing throughout the body. Lupus nephritis (LN), a severe complication, significantly impacts patient outcomes. While genetic, hormonal, and environmental factors contribute, the precise mechanisms driving SLE remain elusive. Understanding these mechanisms is crucial for developing targeted therapies.

Within the complex landscape of SLE, the balance between different types of immune cells plays a pivotal role. T helper 17 (Th17) cells and single immunoglobulin IL-1-related receptor (SIGIRR)+CD4+ T cells are two such cell types. Th17 cells, known for producing the pro-inflammatory cytokine IL-17, are implicated in various autoimmune diseases, including SLE. SIGIRR, on the other hand, acts as an endogenous inhibitor of TLR/ILR signaling, potentially dampening excessive immune responses.

Recent studies suggest that an imbalance between Th17 cells and SIGIRR+CD4+ T cells may contribute to SLE pathogenesis. This article explores the significance of this ratio, drawing on the latest research to explain how these immune cells interact and how their imbalance could be a key factor in SLE development and activity.

The Th17/SIGIRR+CD4+ T Cell Ratio: What Does It Mean for SLE?

Illustration of immune cell balance in SLE

A study published in Biomedical Reports investigated the clinical significance of the Th17/SIGIRR+CD4+ T cell ratio in SLE patients. The researchers analyzed blood samples from 48 SLE patients and 38 healthy controls, focusing on the frequency of Th17 cells in peripheral blood mononuclear cells (PBMCs) and their correlation with clinical data. Flow cytometry was used to quantify these cell populations.

The study revealed several key findings:

Increased Th17 Cells in SLE: SLE patients exhibited significantly higher percentages of Th17 cells in their PBMCs compared to healthy controls.
Elevated Th17 in Active SLE: Patients with active SLE (ASLE) had even higher Th17 cell percentages compared to those with inactive SLE (ISLE).
Th17 and Lupus Nephritis: Patients with lupus nephritis (LN) showed a significant increase in Th17 cell frequency compared to those without LN.
Inverse Correlation: The frequency of Th17 cells was inversely correlated with the frequency of SIGIRR+CD4+ T cells.
Th17/SIGIRR Ratio and Disease Activity: The ratio of Th17 cells to SIGIRR+CD4+ T cells was significantly increased in ASLE patients and inversely correlated with complement components C3 and C4. It was also positively correlated with the SLE disease activity index (SLEDAI) and 24-hour proteinuria.

These findings suggest that Th17 cells and SIGIRR+CD4+ T cells play critical, opposing roles in SLE. An elevated Th17/SIGIRR+CD4+ T cell ratio appears to be associated with increased disease activity and severity.

Implications and Future Directions

The study's results indicate that the balance between Th17 cells and SIGIRR+CD4+ T cells is a significant factor in the pathogenesis of SLE and that this ratio may be a potential therapeutic target. Further research is needed to fully understand the molecular mechanisms involved and to explore how therapies targeting this pathway could improve outcomes for SLE patients. Understanding and modulating the Th17/SIGIRR+CD4+ T cell balance may offer new avenues for personalized treatment strategies in SLE.

About this Article -

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Everything You Need To Know

What exactly is Systemic Lupus Erythematosus (SLE)?

Systemic Lupus Erythematosus (SLE) is an autoimmune condition where the body's immune system mistakenly attacks its own tissues and organs. This leads to the formation of immune complexes that deposit throughout the body, causing inflammation and damage. A severe complication of SLE is lupus nephritis (LN), which affects the kidneys. SLE's development is influenced by genetic, hormonal, and environmental factors, all contributing to the breakdown of self-tolerance.

What are Th17 cells and SIGIRR+CD4+ T cells, and what roles do they play in the immune system?

Th17 cells are a type of immune cell that produces the pro-inflammatory cytokine IL-17. In the context of SLE, elevated levels of Th17 cells contribute to the disease's pathology by promoting inflammation and tissue damage. Conversely, SIGIRR+CD4+ T cells act as endogenous inhibitors of TLR/ILR signaling, which can dampen excessive immune responses. Therefore, SIGIRR helps to regulate and control the immune response, preventing it from becoming overactive.

What is meant by the Th17/SIGIRR+CD4+ T cell ratio, and why is it important in the context of SLE?

The Th17/SIGIRR+CD4+ T cell ratio refers to the balance between pro-inflammatory Th17 cells and regulatory SIGIRR+CD4+ T cells. This balance is crucial in SLE because an imbalance, with a higher proportion of Th17 cells, is associated with increased disease activity and severity. This is because Th17 cells promote inflammation, while SIGIRR+CD4+ T cells help to suppress it.

What does current research reveal about the levels of Th17 cells in SLE patients compared to healthy individuals?

Research indicates that SLE patients tend to have a higher percentage of Th17 cells in their peripheral blood mononuclear cells (PBMCs) compared to healthy individuals. Furthermore, patients with active SLE (ASLE) show even higher Th17 cell percentages, and those with lupus nephritis (LN) exhibit a significant increase in Th17 cell frequency. Importantly, there is an inverse correlation between Th17 cells and SIGIRR+CD4+ T cells, meaning that as Th17 cell levels increase, SIGIRR+CD4+ T cell levels tend to decrease.

How does the Th17/SIGIRR+CD4+ T cell ratio relate to the activity and severity of SLE?

An elevated Th17/SIGIRR+CD4+ T cell ratio is linked to increased disease activity in SLE. This is evidenced by its positive correlation with the SLE disease activity index (SLEDAI) and 24-hour proteinuria, both markers of disease severity. Conversely, the ratio is inversely correlated with complement components C3 and C4, which are important for immune regulation. These findings suggest that modulating this ratio could be a potential therapeutic strategy for managing SLE.