| Presentation preference | Oral presentation |
| Title | A Transcriptional-Network in Blood Dendritic Cells Links a Cytokine-Secreting CD36+CX3CR1+CD1C+ subset to Autoimmunity in the Eye |
| Purpose | CD1c+ conventional dendritic cells (CD1c+ DCs) are increased in blood of noninfectious uveitis patients |
| Methods | RNA-sequencing of CD1c+ dendritic cells in two cohorts of in total 80 patients and controls was conducted. |
| Results | The CD1c+ DCs pool from patients with autoimmune uveitis (n=45) is skewed towards a transcriptional network characterized by surface receptor genes CX3CR1, CCR2, and CD36. We confirmed the association of the transcriptional network with autoimmune uveitis in another case-control cohort (n=35) and demonstrated that it was governed by NOTCH2-RUNX3 signaling. Unbiased flow cytometry analysis based on the transcriptional network identified blood CD1c+ DC subsets that can be distinguished by CX3CR1 and CD36 surface expression. A CD36+CX3CR1+CD1c+ DC subset was diminished in peripheral blood of patients and CD1c+ DCs expressing CD36 and CX3CR1 accumulate locally. The CD36+CX3CR1+CD1c+ DC subset showed a differential capacity to produce cytokines, including TNF-alpha, IL-6, and VEGF, but not IL-23. |
| Conclusion | Collectively, these results show that CD1c+ DC subsets defined on the basis of surface expression of CD36 and CX3CR1 are linked to human autoimmune uveitis and show a differential capacity to secrete proinflammatory mediators that participate in its pathophysiology. |
| Conflict of interest | No |
Authors 1
| Last name | KUIPER |
| Initials of first name(s) | JJW |
| Department | Ophthalmology/CTI |
| City | Utrecht |
| Country | Netherlands |
Authors 2
| Last name | Hiddingh |
| Initials of first name(s) | S |
| Department | CTI/Ophthalmology |
| City | Utrecht |
| Country | Netherlands |
Authors 3
| Last name | Pandit |
| Initials of first name(s) | A |
| Department | CTI/DIGD |
| City | Utrecht |
| Country | Netherlands |
Authors 4
| Last name | Verhagen |
| Initials of first name(s) | FH |
| Department | Ophthalmology |
| City | Utrecht |
| Country | Netherlands |
Authors 5
| Last name | Rijken |
| Initials of first name(s) | R |
| Department | CTI/DIGD |
| City | Utrecht |
| Country | Netherlands |
Authors 6
| Last name | Servaas |
| Initials of first name(s) | NH |
| Department | CTI |
| City | Utrecht |
| Country | Netherlands |
Authors 7
| Last name | Wichers |
| Initials of first name(s) | CGK |
| Department | CTI/DIGD |
| City | Utrecht |
| Country | Netherlands |
Authors 8
| Last name | ten Dam-van Loon |
| Initials of first name(s) | NH |
| Department | Ophthalmology |
| City | Utrecht |
| Country | Netherlands |
Authors 9
| Last name | Radstake |
| Initials of first name(s) | TRDJ |
| Department | DIGD |
| City | Utrecht |
| Country | Netherlands |
Authors 10
| Last name | de Boer |
| Initials of first name(s) | JH |
| Department | Ophthalmology |
| City | Utrecht |
| Country | Netherlands |
