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This abstract is assigned to session 21 - Free Papers IV - Potpourri

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