Different Frequencies of Tc17/Tc1 and Th17/Th1 Cells in Chronic Spontaneous Urticaria

Abstract

Background: Chronic urticaria is associated with an immune dysregulation usually mediated by T lymphocytes. Recently, Th17 and Tc17 have been implicated in autoimmune diseases; however, their role in urticaria is not clear yet. Methods: For the study we recruited 20 patients [10 of them had autoreactive chronic spontaneous urticaria (positive autologous intradermal serum test response, ASST+), and the other 10 were nonautoreactive chronic spontaneous urticaria patients (ASST–)] and 17 healthy age- and gender-matched controls (HG). The frequency and functional activity of Th17/Tc17 and Th1/Tc1 cells were evaluated by flow cytometry and type 2 cytokine mRNA by real-time PCR. Results: Our results demonstrated a significant decrease in Th17 frequency in both chronic urticaria groups compared to HG; regarding the amount of IL-17, at the single cell level, it was reduced in ASST– compared to HG. Concerning the Th1 and Th17 cells producing IFN-γ, IL-2, and TNF-α, a lower frequency was noted in chronic urticaria patients compared to HG. In contrast, a significantly increased frequency of Tc1 cells producing these cytokines was noted in ASST+ compared to HG and ASST–. Also, the frequency of Tc17 cells producing TNF-α was increased in ASST+ compared to HG; however, with respect to the amount of TNF-α, at the single cell level, we found a decrease in ASST+ compared to HG. Regarding type 2 cytokine mRNA, a higher expression was verified in ASST+ compared to HG. Conclusion: Our data suggest a probable involvement of cytotoxic T cells, mainly the Tc1 and Tc17 subsets, in chronic urticaria, particularly in the ASST+ group.

Identification of a Th2‐ and Th17‐skewed immune phenotype in chronic urticaria with Th22 reduction dependent on autoimmunity and thyroid disease markers

“…However, we found no difference in the number of CD117+ mast cells or in the percent of Th1 or Th22 cells of CD3+ cells between these groups. These data support prior reports of a Th2‐skewed and IgE‐related immune phenotype in chronic urticaria and provide evidence that Th17 cells may also be involved in this disease, as in other inflammatory and autoimmune disorders.…”

“…In contrast, cytokines produced by Th1‐ and Th17‐mediated immune pathways, such as IFN‐ γ and IL‐21, have been shown to decrease IgE and subsequently inhibit mast cell activation. A recent study showed decreased levels of serum cytokines produced by Th1 and Th17 cells in chronic urticaria patients. In contrast, other studies have suggested that certain subtypes of IL‐17 that are produced by Th17 cells promote IgE production via B‐cells.…”

“…In contrast, Th1‐mediated immune pathways have been shown to inhibit IgE dependent mast cell activation. While Th17 cells play a role in many inflammatory and autoimmune disorders, the role of this T‐cell subset in chronic urticaria remains unclear; prior reports have suggested both an inhibitory and stimulatory effect on antibody production and subsequent effect on mast cells. While another distinct subset of helper T‐cells, Th22 cells, has been implicated in several inflammatory and autoimmune diseases, including atopic dermatitis and psoriasis, the potential role of Th22 cells in chronic urticaria has not been explored.…”

Different expression patterns of plasma Th1‐, Th2‐, Th17‐ and Th22‐related cytokines correlate with serum autoreactivity and allergen sensitivity in chronic spontaneous urticaria

“…1 The long-lasting course and distressing symptoms have a grave impact on life quality. [3][4][5][6][7][8][9] The activity of T cells is largely dependent on the differentiation of T0 cells into subtypes of CD4+ T-helper (Th) cells, such as Th1, Th2, Th17 and Th22 cells, which can be further grouped based on distinct cytokine profiles. Increasing evidence indicated that inflammation and unbalanced immunity play critical roles in the generation and promotion of the recurrent symptoms.…”

“…[2][3][4][5][6] Inflammatory cells and the cytokines released in the peripheral circulatory micro-environment are proposed to determine the immune response in CSU. [3][4][5][6][7][8][9] The activity of T cells is largely dependent on the differentiation of T0 cells into subtypes of CD4+ T-helper (Th) cells, such as Th1, Th2, Th17 and Th22 cells, which can be further grouped based on distinct cytokine profiles. 10 A complex network of cytokines released by the Th cells is involved in various autoimmune and allergic responses.…”