These findings indicate that TGP inhibits autoimmunity in SLE patients possibly by inducing Treg cell differentiation, which may in turn be due to its ability to regulate the methylation status of the Foxp3 promoter and activate IFN-γ and IL-2 signaling.
Secretion of the inflammatory cytokine IFNγ, together with the acquisition of a T helper 1 (Th1)-like effector phenotype as observed in cancer, infection, and autoimmune diseases, is associated with loss of Treg suppressor function through an unknown mechanism.
Using murine mercury-induced autoimmunity (mHgIA), the severity of inflammation and proinflammatory cytokine expression, including the cellular source of IFN-γ, were assessed at the site of subcutaneous exposure and in secondary lymphoid organs.
In contrast, inhibition of DP IV and APN activities selectively suppresses lymphocyte functions including proliferation and production of the T helper type (Th)1 cytokine IFN-γ, the Th17 cytokine IL-17, as well as TNF-α, and ameliorates autoimmunity in vivo.
This analysis is integrated with the literature on the roles of IFNgamma in mediating a plethora of functions: anti-microbial responses, antigen processing, inflammation, growth suppression, cell death, tumor immunity and autoimmunity.
Co-expression of IFN-γ by Th17 cells has been shown to promote chronic inflammation in several autoimmune diseases and may also contribute to pSS pathogenesis.
These findings explain the bimodal role of IFN-gamma in different models of autoimmune disease and raise questions regarding the clinical relevance of these models.
For that reason, research studies are needed in order to verify the existence of potential IL-18 and IFN-γ gene polymorphisms to utilize as biomarkers of latent autoimmunity.
We conclude that a shift in immunodominance of self-antigenic determinants of Col-V results in induction of IFN-γ and IL-17 with loss of tolerance leading to autoimmunity to Col-V, which leads to chronic lung allograft rejection.
These infiltrating autoreactive T-cells and macrophages release inflammatory cytokines including interferon-gamma in the islets, not only damaging beta-cells but also accelerating CXCL10 generation in residual beta-cells and thus further activating cell-mediated autoimmunity until all beta-cells have been destroyed.
The T-box transcription factor T-bet is a key regulator for the lineage commitment in CD4 Th1 cells and CD8 T cells by activating the hallmark production of interferon-γ, and its expression level is linked to autoimmune diseases.
γd T cells have emerged as major sources of the proinflammatory cytokines interleukin-17 (IL-17) and interferon-γ (IFNγ) in multiple models of infection, cancer and autoimmune disease.
Besides being crucial for mycobacterial control, the IFN-gamma/IL-12 pathway is also involved in the pathogenesis of autoimmune disease as well as tumor development and control.
In addition to the pivotal role of IFNgamma in host defense, its excessive release has been associated with the pathogenesis of chronic inflammatory and autoimmune diseases.
Multiple type I interferons and interferon-γ (IFN-γ) are expressed under physiological conditions and are increased by stress and infections, and in autoinflammatory and autoimmune diseases.
Administration of cDNA encoding soluble IFN-gamma receptor (IFN-gamma R)/IgG-Fc fusion proteins, soluble TNF-alpha receptors, or IL-1 receptor antagonist (IL-1ra), protects against either lupus, various forms of arthritis, autoimmune diabetes, or other autoimmune diseases.
To further define their roles in systemic autoimmunity, IL-4 and IFN-gamma gene knockout mice were studied for susceptibility to the prototypic Th2-mediated mercury-induced autoimmunity.
An epigenetic mechanism for high, synergistic expression of indoleamine 2,3-dioxygenase 1 (IDO1) by combined treatment with zebularine and IFN-γ: potential therapeutic use in autoimmune diseases.
Correlation analysis showed dependency of accelerated autoimmunity and β cell destruction on increased IFN-γ, IL-12 and IL-17 versus decreased IL-4, -6 and -13.
Our findings highlight a role for Mal outside the TLR system and imply that genetic variation in TIRAP may be linked to other IFN-γ-related diseases including autoimmunity and cancer.
The evidence suggests that T cells can produce TNF and have the potential to deliver by themselves the dual and synergistic signals of TNF/LT and IFN-gamma to target cells, a process which may be of importance in the pathogenesis of human autoimmunity.