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In this study we investigated the role of blood CD1c(+) myeloid dendritic cells 1 (mDC1), a key mDC subtype, in patients with autoimmune uveitis. We observed a significant increase of blood CD1c(+) mDC1 in uveitis patients. The increased CD1c(+) mDC1 exhibited high HLADR expression and less antigen uptake. CD1c(+) mDC1 were divided into two subpopulations. CD1c(hi) mDC1 subpopulation showed less antigen uptake and higher HLADR expression compared to CD1c(lo) mDC1 subpopulation. Importantly, the CD1c(hi) mDC1 subpopulation was increased in uveitis patients. In vitro, mature monocyte-derived dendritic cells (MoDCs), characterized by lower levels of antigen uptake, induced more CD4(+)CD62L(-) T helper cell proliferation. The mature phenotype and function of CD1c(+) mDC1 were regulated by TNFα via a p38 MAPK-dependent pathway. These data show that alterations in the systemic immune response are involved in the pathogenesis of autoimmune uveitis and invite the therapeutic possibility of attenuating uveitis by manipulating blood CD1c(+) mDC1., (Published by Elsevier Inc.)

Annexin-A1 (Anx-A1) is an endogenous anti-inflammatory molecule and while described as a repressor of innate immune responses, the role of Anx-A1 in adaptive immunity, and in particular in T helper (Th) cell responses, remains controversial. We have used a T-cell mediated mouse model of retinal autoimmune disease to unravel the role of Anx-A1 in the development of autoreactive Th cell responses and pathology. RBP1-20-immunized C57BL/6 Anx-A1(-/-) mice exhibit significantly enhanced retinal inflammation and pathology as a result of an uncontrolled proliferation and activation of Th17 cells. This is associated with a limited capacity to induce SOCS3, resulting in un-restricted phosphorylation of STAT3. RBP1-20-specific CD4(+) cells from immunized Anx-A1(-/-) animals generated high levels of Th17 cells-associated cytokines. Following disease induction, daily systemic administration of human recombinant Anx-A1 (hrAnx-A1), during the afferent phase of disease, restrained autoreactive CD4(+) cell proliferation, reduced expression of pro-inflammatory cytokines IL-17, IFN-γ and IL-6 and attenuated autoimmune retinal inflammatory disease. Furthermore, in man, Anx-A1 serum levels when measured in active uveitis patient sera were low and associated with the detection of IgM and IgG anti-Anx-A1 antibodies when compared to healthy individuals. This data supports Anx-A1 as an early and critical regulator of Th17 cell driven autoimmune diseases such as uveitis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: Myeloid dendritic cells (mDCs) play an important role in autoimmune diseases. However, the role of blood CD1c(+) myeloid dendritic cells 1 (mDC1s), the subset of human blood mDCs, is not well understood in noninfectious uveitis., Methods: Fresh peripheral blood samples from human noninfectious uveitis patients (n = 32) and healthy controls (HCs) (n = 64) were stained with FITC-Lineage 1 (Lin1), PERCP-HLADR, and PE-CD1c antibodies. The levels of mDC1 were quantified by using flow cytometric analysis. Longitudinal data from patients (n = 16) were analyzed to correlate the levels of mDC1 with disease activity., Results: Blood CD1c(+) mDC1 and its subpopulation, CD1c(hi) mDC1, were increased in uveitis patients compared with HCs. Longitudinal data demonstrated that both the CD1c(+) mDC1 and CD1c(hi) mDC1 subpopulation reflected a dynamic change in clinical uveitis activity: CD1c expression was increased in active uveitis but decreased when uveitis became inactive., Conclusions: Given these observations, an alteration in blood CD1c(+) mDC1 and the CD1c(hi) mDC1 subpopulation could be a potential biomarker to monitor clinical uveitis activity within patients., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

Despite a lack of robust evidence, anti-TNF therapies are in wide use for the treatment of noninfectious ocular inflammatory diseases. There is a clear rationale, based on mechanistic and preclinical efficacy data, for their use in posterior segment intraocular inflammation. However, their increasing use for other indications has been largely extrapolated from the benefit observed in autoinflammatory and autoimmune systemic diseases. Given their cost and the potential for significant adverse events, this review highlights the evidence for their continued use, possibilities for switching anti-TNF agents, and ways of reducing the risk of therapy. [ABSTRACT FROM AUTHOR]