Abnormal NF-κB function characterizes human type 1 diabetes dendritic cells and monocytes

Mollah, Zia U.A., Pai, Saparna, Moore, Craig, O'Sullivan, Brendan J., Harrison, Matthew J., Peng, Judy, Phillips, Karen, Prins, Johannes B., Cardinal, John, and Thomas, Ramjeny (2008) Abnormal NF-κB function characterizes human type 1 diabetes dendritic cells and monocytes. The Journal of Immunology, 180 (5). pp. 3166-3175.

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Abstract

Dendritic cell (DC) differentiation is abnormal in type 1 diabetes mellitus (T1DM). However, the nature of the relationship between this abnormality and disease pathogenesis is unknown. We studied the LPS response in monocytes and monocyte-derived DCs isolated from T1DM patients and from non-T1DM controls. In T1DM patients, late LPS-mediated nuclear DNA binding by RelA, p50, c-Rel, and RelB was impaired as compared with type 2 DM, rheumatoid arthritis, and healthy subjects, associated with impaired DC CD40 and MHC class I induction but normal cytokine production. In TIDM monocytes, RelA and RelB were constitutively activated, and the src homology 2 domain-containing protein tyrosine phosphatase (SHP-1), a negative regulator of NF-κB, was overexpressed. Addition of sodium stibogluconate, a SHP-1 inhibitor, to DCs differentiating from monocyte precursors restored their capacity to respond to LPS in ∼60% of patients. The monocyte and DC NF-κB response to LPS is thus a novel phenotypic and likely pathogenetic marker for human T1DM. SHP-1 is at least one NF-κB regulatory mechanism which might be induced as a result of abnormal inflammatory signaling responses in T1DM monocytes.

Item ID: 50154
Item Type: Article (Refereed Research - C1)
ISSN: 1550-6606
Date Deposited: 12 Sep 2017 05:47
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060111 Signal Transduction @ 34%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 33%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 33%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 33%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920104 Diabetes @ 34%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 33%
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