| First Author | Strainic MG | Year | 2019 |
| Journal | Am J Pathol | Volume | 189 |
| Issue | 7 | Pages | 1386-1401 |
| PubMed ID | 31103439 | Mgi Jnum | J:278366 |
| Mgi Id | MGI:6323288 | Doi | 10.1016/j.ajpath.2019.04.008 |
| Citation | Strainic MG, et al. (2019) CD55 Is Essential for CD103(+) Dendritic Cell Tolerogenic Responses that Protect against Autoimmunity. Am J Pathol 189(7):1386-1401 |
| abstractText | 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-beta production and presentation, as well as integrin beta6/integrin beta8 associated with Treg and CD103(+) DC transforming growth factor-beta release. Thus, DAF is required for the properties of CD103(+) DCs and their naive CD4(+) cell partners that together program tolerance. |
