Th1/Th17-Related Cytokines and Chemokines and Their Implications in the Pathogenesis of Pemphigus Vulgaris

Abstract

Pemphigus vulgaris (PV) is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-3. Despite the variety of findings, the chemokine and cytokine profiles that characterize the immune response in the disease are still poorly explored. Thus, 20 PV patients and 20 controls were grouped according to gender, ethnicity, place of residence, and clinical parameters of the disease. Then, the levels of chemokines and of Th1/Th2/Th17/Treg/Th9/Th22-related cytokines were assessed in the serum. PV patients had higher levels of inflammatory Th1/Th17 cytokines (IFN-γ, IL-17, and IL-23), as well as higher levels of CXCL8 and reduced levels of Th1/Th2-related chemokines (IP-10 and CCL11). However, no differences in the levels of IL-2, IL-6, TNF-α, IL-1β, IL-4, IL-9, IL-12, TGF-β, IL-33, MCP-1, RANTES, and MIP-1α were found between PV patients and their control counterparts. Furthermore, PV patients with skin lesions had higher serum levels of IL-6 and CXCL8 when compared to PV patients without lesions. Taken together, our findings describe the role of cytokines and chemokines associated with Th1/Th17 immune response in PV patients. Finally, these data are important for better understanding of the immune aspects that control disease outcome, and they may also provide important information about why patients develop autoantibodies against desmogleins.

Figure 1

Serum profile of T cell-derived cytokines in Pemphigus vulgaris. Levels of (a) IFN-γ, (b) IL-17, (c) IL-10, and (d) IL-22 in Healthy Donors (⬤) and Pemphigus vulgaris patients (■). Error bars represent median ± SD. ^∗p < 0.05; ^∗∗p < 0.01; ^∗∗∗p < 0.001; ^∗∗∗∗p < 0.0001; Mann–Whitney test. (e) Radar plot representation of serum T cell-derived cytokine profile. The lines highlight the fold change in cytokine levels in Pemphigus vulgaris patients (gray line) in relation to Healthy Donors (black line). Data were obtained by calculating the ratio between the median concentration of each cytokine in the Pemphigus vulgaris group and in the healthy group.

Figure 2

Serum profile of other proinflammatory cytokines in Pemphigus vulgaris. Levels of (a) IL-2, (b) TNF-α, (c) IL-12, (d) IL-6, (e) IL-23, (f) IL-13, (g) IL-5, (h) IL-15, and (i) IL-33 in Healthy Donors (⬤) and Pemphigus vulgaris patients (■). Error bars represent median ± SD. ^∗p < 0.05; ^∗∗p < 0.01; ^∗∗∗∗p < 0.0001; Mann–Whitney test. (j) Radar plot representation of serum proinflammatory cytokine profile. The lines highlight the fold change in cytokine levels in Pemphigus vulgaris patients (gray line) in relation to Healthy Donors (black line). Data were obtained by calculating the ratio between the median concentration of each cytokine in the Pemphigus vulgaris group and in the healthy group.

Figure 3

Serum profile of chemokines in Pemphigus vulgaris. Levels of (a) CCL-2/MCP-1, (b) CCL5/RANTES, (c) CCL11/Eotaxin, (d) CXCL8/IL-8, and (e) CCL10/IP-10 in Healthy Donors (⬤) and Pemphigus vulgaris patients (■). Error bars represent median ± SD. ^∗∗∗p < 0.001; ^∗∗∗∗p < 0.0001; Mann–Whitney test. (f) Radar plot representation of serum chemokine pattern. The lines highlight the fold change in cytokine levels in Pemphigus vulgaris patients (gray line) in relation to controls (black line). Data were obtained by calculating the ratio between the median concentration of each cytokine in the Pemphigus vulgaris group and in the control group.

Figure 4

Skin lesions in Pemphigus vulgaris are associated with higher levels of IL-6 and CXCL8. Levels of (a) IL-2, (b) IL-6, and (c) CXL8 (IL-8) in Pemphigus vulgaris (PV) patients with no skin lesions (⬤) and PV patients with skin lesions (■). (d) Correlation between the frequency of lesions and time of treatment and (e) correlation between the frequency of skin lesions and dosage of glucocorticoids used to treat PV patients. Error bars represent median ± SD. ^∗p < 0.05, Mann–Whitney test was used in (a–c). The Spearman correlation test was used to evaluate the strength of association between the variables (d and e).