Increased CD1c+ mDC1 with mature phenotype regulated by TNFα–p38 MAPK in autoimmune ocular inflammatory disease

Chen, Ping; Denniston, Alastair K; Hannes, Susan; Tucker, William R; Wei, Lai; Liu, Baoying; Xiao, Tiaojiang; Hirani, Sima; Li, Zhiyu; Jawad, Shayma; Si, Han; Lee, Richard W.; Sen, H. Nida; Nussenblatt, Robert B.

doi:10.1016/j.clim.2015.03.002

Cited by 9 publications

(18 citation statements)

References 42 publications

(47 reference statements)

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“…CD1c + mDCs and plasmacytoid dendritic cells (pDCs) were identified as the Lineage Cocktail 1 (Lin1) − HLADR + CD1c + and Lin1 − HLADR + CD303 + populations, respectively, as previously reported. 1 , 8 , 9 Antibodies were purchased from Miltenyi Biotec (San Diego, CA, USA) or BD Biosciences (San Diego, CA, USA). The same procedure for handling blood samples was used for HCs and patients.…”

Section: Methodsmentioning

confidence: 99%

“…CD1c + myeloid dendritic cells (mDCs) are one of the major DC subtypes in humans. 1 , 8 We have previously observed that proportions of CD1c + mDCs are increased in uveitis patients compared to healthy controls (HCs) in a small cohort. 9 Furthermore, a high level of CD1c expression on mDCs is strongly associated with increased HLADR expression and decreased mDC antigen uptake, suggesting that CD1c + mDCs are activated and mature in uveitis patients.…”

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confidence: 99%

“…Noninfectious uveitis (uveitis) consists of a group of inflammatory eye diseases that often require local and/or systemic immunosuppression to adequately control intraocular inflammation and prevent blindness. 1 While the pathophysiology is not completely understood, experimental models of autoimmune uveitis suggest that CD4 + T-cell activation by uveitis-specific antigens plays a major role. 2 Therefore, both topical and systemic immunosuppressive treatments have been used extensively to control uveitis in patients.…”

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confidence: 99%

“…Dendritic cells (DCs) present antigens to T cells to induce adaptive immune responses. 1 , 7 Different types of DCs play different roles in autoimmune disease. CD1c + myeloid dendritic cells (mDCs) are one of the major DC subtypes in humans.…”

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confidence: 99%

“… 9 Furthermore, a high level of CD1c expression on mDCs is strongly associated with increased HLADR expression and decreased mDC antigen uptake, suggesting that CD1c + mDCs are activated and mature in uveitis patients. 1 …”

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confidence: 99%

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Elevated CD1c⁺Myeloid Dendritic Cell Proportions Associate With Clinical Activity and Predict Disease Reactivation in Noninfectious Uveitis

Chen

Urzua

Knickelbein

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeTo test the association between elevated proportions of CD1c+ myeloid dendritic cells (mDCs) and disease activation/reactivation in noninfectious uveitis.MethodsNoninfectious uveitis patients (n = 89) and healthy controls (n = 111) were recruited. The proportion of CD1c+ mDCs in the total dendritic cell (DC) population of peripheral blood was measured by flow cytometry (CD1c+ mDCs gated on Lineage 1+HLADR+ DCs). Disease activity was assessed per Standardization of Uveitis Nomenclature criteria. Uveitis reactivation was ascribed to clinically quiescent patients who developed reactivation of intraocular inflammation within 6 months.ResultsThe proportions of CD1c+ mDCs were increased in noninfectious uveitis patients, especially in active disease, compared to healthy controls. This CD1c+ mDC elevation was not associated with underlying systemic diseases, anatomic locations of uveitis, medications, or demographic factors. Longitudinal data showed that the dynamics of CD1c+ mDC levels were correlated with disease activity. The average proportion of CD1c+ mDCs in active uveitis patients was 60% so we set this as the cutoff between high and low CD1c+ mDC levels. Although 74% of quiescent patients had low proportions of CD1c+ mDCs, 26% still had high proportions. Quiescent patients with high CD1c+ mDC proportions showed increased risk of disease reactivation, compared to quiescent patients with low CD1c+ mDC proportions.ConclusionsIncreased proportions of CD1c+ mDCs were associated with clinical activity, and quiescent patients with elevated CD1c+ mDCs were more likely to undergo reactivation. This suggests that CD1c+ mDC proportion may be a potential biomarker for assessing clinical activation and reactivation in noninfectious uveitis.

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Section: Methodsmentioning

confidence: 99%

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