Discrimination of CD4+ T cells that lack CCR7 expression revealed that CCR7- CD4+ memory T cells and effectors are producers of intracellular TNFα, IL-13 and IL-4, particularly in dcSSc.
How these different cell types interact to contribute to SSc is complicated, and can involve cell-to-cell interactions and communication via cytokines, including transforming growth factor (TGF)-β, interleukin (IL)-6 and IL-4.
The levels of serum IL-35 were positively correlated with IL-4 (P = 0.036) and tended to be positively associated with the frequency of Tregs in SSc patients (P = 0.054).
After anti-CD3/CD28 stimulation, higher levels of IL-2 and IL-4 were observed in SSc patients with lung fibrosis (p = 0.01 and 0.006, respectively), and higher levels of IL-10 (p = 0.04) and IL-4 (p = 0.04) in patients with digital ulcers.
As with animal findings, the frequency of pDCs in the lungs of patients with systemic sclerosis correlated with the severity of lung disease and with the frequency of CD4+ and IL-4+ T cells in the lung.
Polymorphisms in the interleukin 4, interleukin 13, and corresponding receptor genes are not associated with systemic sclerosis and do not influence gene expression.
While the causes of fibrosis in scleroderma are unknown, cytokines such as TGF-beta, IL-4 and IL-13, play a crucial role in the stimulation of collagen production have been implicated in the disease process.
Interleukin 4 and prolonged hypoxia induce a higher gene expression of lysyl hydroxylase 2 and an altered cross-link pattern: important pathogenetic steps in early and late stage of systemic scleroderma?
Interleukin-2, interleukin-4, interleukin-6, and transforming growth factor-beta have been implicated as cytokines that may be involved in the pathogenesis of systemic sclerosis.