Professional Documents
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Lymphocyte circulation
SMRT
2,3,7,8tetrachloro dibenzo-pdioxin
6formylindolo[ 3,2b]carbazole
IRF-1
IRF-4 NFAT
IRF-4 STAT 3
CTLA
RPE CTLA-2 functions as a TGF promoter and cathepsin L inhibitor in the eye. Cathepsin Linhibited T cells eventually convert to Treg cells that acquire regulatory functions. CTLA-2 and TGF, are upregulated when intraocular inflammation occurs in immune privileged sites such as the eyes. CTLA-2 is most strongly expressed in the brain, the placenta, and the eyes. CTLA-2 induces Foxp3-positive regulatory T cells.
RPE cells from the posterior segment of the eye primarily use soluble inhibitory factors to promote the induction of Treg cells. Cultured CE cells that can convert T cells to Foxp3 Treg cells express CTLA-2. Intense staining was observed on the corneal endothelium and epithelium, iris, and ciliary body for CTLA-2. CTLA-2overexpressing CE cells significantly produced TGF1. Therefore, CTLA-2 produced by corneal endothelium promotes the activation of TGF.
TLRs
nTreg cells treated with LTA, but not with CpG2007, expressed IFN-c and IL-10 mRNA, but not TGF-b. Treatment with TLR2 Ligand LTA Significantly Reverses the Immunosuppressive Function of CD4CD25 nTreg Cells. TLR2 Ligand Pam3CSK4, but Not LTA, Affects Foxp3 Expression in Conjunctiva-Resident CD4CD25 nTreg Cells.
IL-2 is also essential to maintain self-tolerance, as IL-2- and IL2 receptor-deficient mice exhibit lethal autoimmunity. Antigen-activated T cells expand in response to IL-2 and become very sensitive to apoptosis if restimulated by antigens through their T cell receptor (TCR). This phenomenon was coined as activation induced cell death (AICD). Complement and uveitis. Ligation of TLR9 induced on human IL-10 secreting Tregs by 1,25-dihydroxyvitamin D3 abrogates regulatory function. Synergistic effect of TGF- and RA inhibits the early CTLA-4 expression on effector cells, but instead allows its later expression by cells committed to the Foxp3 lineage. Retinoic Acid might also synergize with Smads that act downstream of TGF- receptor signaling, and/or with the transcription factor Runx3, which is involved in CD103 induction and physically interacts with Smads to cooperate in TGF- mediated signaling.
Th 17 cells
Tregs
IL-10 Tr 1
IL-10 and TGFb(+++). IFN-a ,IL-5 (++). IL-2/IL-4(+/0). Th1 and Th2 TGF-b (++)
IL-4
Th 3 Inhibit EAE
Natural Tregs
Treg
via a mechanism which remains to be defined, but requires direct cell-to-cell contact and may involve signals through CTLA-4 and GITR. Suppression independent of CD25. Tregs provide peripheral tolerance. TNF, TNFR II and Tregs.
GC inhibit the production of pro-inflammatory (interleukin [IL]-1, IL-6, tumor necrosis factor [TNF]-a) and Th1-related cytokines (IL-2, IL-12, cinterferon [IFN-c], granulocyte macrophage colony-stimulating factor [GMCSF]), as well as inflammatory mediators, such as prostaglandin and nitric oxide, and enhance the production of anti-inflammatory cytokines (IL-4, IL-10). GC also suppress the proliferation and function of cytotoxic T cells. GC inhibit antigen presentation by suppressing the maturation of dendritic cells and reducing the expression of major histocompatibility complex (MHC) class II molecules.1 GC suppress cell trafficking by inhibiting the production of chemoattractants (IL-5, IL-8, regulated on activation, normal T cell expressed and secreted [RANTES], eotaxin, monocyte chemotactic protein-1 [MCP-1]) and the expression of cell adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], E-selectin). Furthermore, GC induce the apoptosis of T cells and thymocytes through increasing the expression of Bad, Bcl-XS and Bcl-XL genes.
With this background information we have found that during uveitis major changes occur in the micro environment of the eye and study of these changes may provide details of immunology of this group of diseases.