| Popis: |
Recent studies traced inflammatory bowel disease in some patients to deficiency of CD55 [decay-accelerating factor (DAF)], but the mechanism underlying the linkage remained unclear. Herein, we studied the importance of DAF in enabling processes that program tolerance in the gut and the eye, two immune-privileged sites where immunosuppressive responses are continuously elicited. Unlike oral feeding or ocular injection of ovalbumin in wild-type (WT) mice, which induced dominant immune tolerance, identical treatment of DAF(–/–) mice or DAF(–/–) to WT bone marrow chimeras did not. While 10% to 30% of mesenteric and submandibular lymph node CD4(+) cells became robust T-regulatory cells (Tregs) in WT forkhead box P3 (Foxp3)–green fluorescent protein mice, few in either site became Tregs with little suppressor activity in DAF(–/–) Foxp3–green fluorescent protein mice. Phenotyping of CD103(+) dendritic cells (DCs) from the ovalbumin-fed DAF(–/–) mice showed impaired expression of inducer of costimulation (ICOS) ligand, programmed death receptor 1-ligand 1 (PD1-L1), CxxxC chemokine receptor 1 (Cx3CR1), CCR7, and CCR9. Analyses of elicited DAF(–/–) Foxp3(+) Tregs showed reduced expression of interferon regulatory factor 8 (IRF-8)/aldehyde dehydrogenase 1 family member A2 (Aldh1a2) and glycoprotein A repetitions predominant/latency-associated protein associated with Treg transforming growth factor-β production and presentation, as well as integrin β6/integrin β8 associated with Treg and CD103(+) DC transforming growth factor-β release. Thus, DAF is required for the properties of CD103(+) DCs and their naïve CD4(+) cell partners that together program tolerance. |
