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Enhanced CCR5+/CCR3+ T helper cell ratio in patients with active cutaneous lupus erythematosus
Insights
Cutaneous lupus erythematosus (CLE) is linked to increased interferon-alpha (IFNα), promoting a Th1 immune response. Active CLE patients show a higher CCR5/CCR3 T-helper cell ratio, correlating with disease activity.
Area of Science:
- Immunology
- Dermatology
- Molecular Biology
Background:
- Cutaneous lupus erythematosus (CLE) exhibits elevated serum and tissue interferon-alpha (IFNα) levels.
- IFNα is known to promote a Th1-biased immune response.
Purpose of the Study:
- To investigate the hypothesis that active CLE is associated with a Th1-associated chemokine receptor profile.
- To explore the relationship between chemokine receptor expression, type I IFN activity, and CLE disease activity.
Main Methods:
- Peripheral blood mononuclear cells were isolated from CLE patients and healthy controls.
- Flow cytometry was used to analyze T helper cell expression of CCR5 (Th1) and CCR3 (Th2).
- Intracellular MxA protein levels, an indicator of type I IFN activity, were measured.
Main Results:
- Patients with active CLE showed significantly increased CCR5 expression and decreased CCR3 expression compared to controls.
- MxA protein levels were elevated in all CLE subtypes, highest in those with widespread skin lesions.
- The CCR5/CCR3 ratio correlated with MxA levels and disease activity in CLE patients.
Conclusions:
- Active CLE is associated with a systemic type I IFN effect.
- This IFN effect appears to induce a shift towards a Th1-associated chemokine receptor profile in T helper cells.
- The CCR5/CCR3 T-helper cell ratio may serve as an indirect biomarker for CLE disease activity.
Abstract:
Cutaneous lupus erythematosus (CLE) is characterized by enhanced interferon α (IFNα) levels in serum and in tissue. Since IFNα promotes a Th1-biased immune response, we hypothesized that a Th1-associated chemokine receptor profile should be a typical finding in patients with active CLE. Therefore, peripheral blood mononuclear cells were isolated from patients with different CLE subsets (n = 15), healthy controls (n = 13) and patients under immunotherapy with IFNα (n = 7). T helper cells were analysed by flow cytometry for the expression of the chemokines receptor CCR5, indicative for Th1 cells, and of CCR3, indicating Th2. In addition, intracellular levels of the type I IFN-inducible MxA protein were measured. Patients with widespread active CLE skin lesions had a significantly increased expression of CCR5, whereas expression of CCR3 was decreased when compared with healthy controls. MxA expression was significantly enhanced in all investigated CLE subtypes, with the highest levels in patients with widespread skin lesions. The enhanced CCR5/CCR3 ratio closely correlated with the MxA levels in peripheral lymphocytes and with disease activity. Our analyses revealed that active CLE is associated with a systemic type I IFN effect that appears to induce a shift towards a Th1-associated chemokine receptor profile. The CCR5/CCR3 T-helper cell ratio might therefore represent an indirect marker for the disease activity in CLE.

