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

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

doi:10.1016/j.clim.2015.03.002

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

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

Immunology and Immunotherapy

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Abstract

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.

Original language	English
Pages (from-to)	35-46
Number of pages	12
Journal	Clinical Immunology
Volume	158
Issue number	1
Early online date	14 Mar 2015
DOIs	https://doi.org/10.1016/j.clim.2015.03.002
Publication status	Published - 1 May 2015

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10.1016/j.clim.2015.03.002

Chen_et_al_Increased_CD1c+_mDC1_Clinical_Immunology_2015
NOTICE: this is the author’s version of a work that was accepted for publication in Clinical Immunology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Clinical Immunology, Vol 158, Issue 1, DOI: 10.1016/j.clim.2015.03.002. Eligibility for repository checked April 2015
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Chen, P., Denniston, A., Hannes, S., Tucker, W., Wei, L., Liu, B., Xiao, T., Hirani, S., Li, Z., Jawad, S., Si, H., Lee, R. W. J., Nida Sen, H., & Nussenblatt, R. B. (2015). Increased CD1c⁺ mDC1 with mature phenotype regulated by TNFα–p38 MAPK in autoimmune ocular inflammatory disease. Clinical Immunology, 158(1), 35-46. Advance online publication. https://doi.org/10.1016/j.clim.2015.03.002

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

abstract = "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. CD1chi mDC1 subpopulation showed less antigen uptake and higher HLADR expression compared to CD1clo mDC1 subpopulation. Importantly, the CD1chi 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.",

author = "Ping Chen and Alastair Denniston and Susan Hannes and William Tucker and Lai Wei and Baoying Liu and Tiaojiang Xiao and Sima Hirani and Zhiyu Li and Shayma Jawad and Han Si and Lee, {Richard W.j.} and {Nida Sen}, H. and Nussenblatt, {Robert B.}",

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doi = "10.1016/j.clim.2015.03.002",

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T1 - Increased CD1c+ mDC1 with mature phenotype regulated by TNFα–p38 MAPK in autoimmune ocular inflammatory disease

AU - Chen, Ping

AU - Denniston, Alastair

AU - Hannes, Susan

AU - Tucker, William

AU - Wei, Lai

AU - Liu, Baoying

AU - Xiao, Tiaojiang

AU - Hirani, Sima

AU - Li, Zhiyu

AU - Jawad, Shayma

AU - Si, Han

AU - Lee, Richard W.j.

AU - Nida Sen, H.

AU - Nussenblatt, Robert B.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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. CD1chi mDC1 subpopulation showed less antigen uptake and higher HLADR expression compared to CD1clo mDC1 subpopulation. Importantly, the CD1chi 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.

AB - 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. CD1chi mDC1 subpopulation showed less antigen uptake and higher HLADR expression compared to CD1clo mDC1 subpopulation. Importantly, the CD1chi 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.

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DO - 10.1016/j.clim.2015.03.002

M3 - Article

SN - 1521-6616

VL - 158

SP - 35

EP - 46

JO - Clinical Immunology

JF - Clinical Immunology

IS - 1

ER -

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

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