A Replication Study Confirms the Association of Dendritic Cell Immunoreceptor (DCIR) Polymorphisms with ACPA - Negative RA in a Large Asian Cohort

Guo, Jianping; Wu, Xinyu; Too, Chun Lai; Yin, Fangrui; Lu, Xuedong; He, Jing; Li, Ru; Liu, Xu; Murad, Shahnaz; Padyukov, Leonid; Li, Zhanguo

doi:10.1371/journal.pone.0041228

Cited by 22 publications

(17 citation statements)

References 20 publications

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“…Therefore, the finding that DCIR plays a major role in limiting CHIKV-induced inflammatory disease represents the first demonstration that a CLR plays a major role in the pathogenesis of alphavirus-induced arthritis. This result is consistent with prior studies which have shown that DCIR polymorphisms are associated with susceptibility to rheumatoid arthritis in humans (46,66,67) and modulate the severity of collagen-induced arthritis in mice (44,62). It is interesting that these studies showed that increased DCIR expression correlates with rheumatoid arthritis occurrence and severity.…”

Section: Discussionsupporting

confidence: 92%

Dendritic Cell Immunoreceptor Regulates Chikungunya Virus Pathogenesis in Mice

Long

Whitmore

Ferris

et al. 2013

J Virol

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c Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for recent epidemic outbreaks of debilitating disease in humans. Alphaviruses are known to interact with members of the C-type lectin receptor family of pattern recognition proteins, and given that the dendritic cell immunoreceptor (DCIR) is known to act as a negative regulator of the host inflammatory response and has previously been associated with rheumatoid arthritis, we evaluated DCIR's role in response to CHIKV infection. Although we observed an increase in the proportion of dendritic cells at the site of CHIKV infection at 24 to 36 h postinfection, these cells showed decreased cell surface DCIR, suggestive of DCIR triggering and internalization. In vitro, bone marrow-derived dendritic cells from DCIR-deficient (DCIR ؊/؊ ) mice exhibited altered cytokine expression following exposure to CHIKV. DCIR ؊/؊ mice exhibited more severe disease signs than wild-type C57BL6/J mice following CHIKV infection, including a more rapid and more severe onset of virus-induced edema and enhanced weight loss. Histological examination revealed that DCIRdeficient animals exhibited increased inflammation and damage in both the fascia of the inoculated foot and the ankle joint, and DCIR deficiency skewed the CHIKV-induced cytokine response at the site of infection at multiple times postinfection. Early differences in virus-induced disease between C57BL6/J and DCIR ؊/؊ mice were independent of viral replication, while extended viral replication correlated with enhanced foot swelling and tissue inflammation and damage in DCIR ؊/؊ compared to C57BL6/J mice at 6 to 7 days postinfection. These results suggest that DCIR plays a protective role in limiting the CHIKV-induced inflammatory response and subsequent tissue and joint damage.

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Section: Discussionsupporting

confidence: 92%

Dendritic Cell Immunoreceptor Regulates Chikungunya Virus Pathogenesis in Mice

Long

Whitmore

Ferris

et al. 2013

J Virol

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“…Because DCIR polymorphisms were associated with several noninfectious inflammatory disorders in humans (17)(18)(19), we asked whether DCIR could play a part in modulating immunity in the context of a chronic inflammation of infectious nature, namely TB. We first found that DCIR is expressed at the periphery of lung granulomas in M. tuberculosis-infected nonhuman primates (NHPs), a model that closely mimics TB in humans, during both asymptomatic infection and active TB disease (SI Appendix, Fig.…”

Section: Dcir Expressionmentioning

confidence: 99%

C-type lectin receptor DCIR modulates immunity to tuberculosis by sustaining type I interferon signaling in dendritic cells

Troegeler

Mercier

Cougoule

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Immune response against pathogens is a tightly regulated process that must ensure microbial control while preserving integrity of the infected organs. Tuberculosis (TB) is a paramount example of a chronic infection in which antimicrobial immunity is protective in the vast majority of infected individuals but can become detrimental if not finely tuned. Here, we report that C-type lectin dendritic cell (DC) immunoreceptor (DCIR), a key component in DC homeostasis, is required to modulate lung inflammation and bacterial burden in TB. DCIR is abundantly expressed in pulmonary lesions in Mycobacterium tuberculosis-infected nonhuman primates during both latent and active disease. In mice, we found that DCIR deficiency impairs STAT1-mediated type I IFN signaling in DCs, leading to increased production of IL-12 and increased differentiation of T lymphocytes toward Th1 during infection. As a consequence, DCIR-deficient mice control M. tuberculosis better than WT animals but also develop more inflammation characterized by an increased production of TNF and inducible NOS (iNOS) in the lungs. Altogether, our results reveal a pathway by which a C-type lectin modulates the equilibrium between infection-driven inflammation and pathogen’s control through sustaining type I IFN signaling in DCs.

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“…The novel associations at PRL and NFIA add to the list of suggestive or confirmed anti‐CCP–negative RA susceptibility loci: PTPN22, TNFAIP3, C5orf30, STAT4, BLK 8, SPP1 16, CLEC16A 17, IRF5 18, DCIR 19, 20, CLYBL 14, SMIM21 14, and ANKRD55 21. However, only a few of those associations have been independently replicated or confirmed at genome‐wide levels of significance.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously tested markers of anti‐CCP–positive RA for their association with anti‐CCP–negative RA 8 and reported that several anti‐CCP–positive RA susceptibility loci (e.g., AFF3, CCR6, CCL21, IL2RA, and CD28 ) were not shared with anti‐CCP–negative RA, while markers at TNFAIP3, C5orf30, STAT4, ANKRD55, BLK, and PTPN22 were associated with both anti‐CCP–positive and anti‐CCP–negative RA. In addition, CLYBL 14, SMIM21 14, SPP1 16, CLEC16A 17, IRF5 18, and DCIR 19, 20 have been reported to be associated with anti‐CCP–negative RA. Of the markers reported to be associated with anti‐CCP–negative RA, only CLYBL 14, SMIM21 14, and ANKRD55 21 have been independently replicated or confirmed at genome‐wide levels of significance.…”

mentioning

confidence: 99%

Replication of Associations of Genetic Loci Outside the HLA Region With Susceptibility to Anti–Cyclic Citrullinated Peptide–Negative Rheumatoid Arthritis

Massey

Duffus

Eyre

et al. 2016

Arthritis & Rheumatology

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ObjectiveGenetic polymorphisms within the HLA region explain only a modest proportion of anti–cyclic citrullinated peptide (anti‐CCP)–negative rheumatoid arthritis (RA) heritability. However, few non‐HLA markers have been identified so far. This study was undertaken to replicate the associations of anti‐CCP–negative RA with non‐HLA genetic polymorphisms demonstrated in a previous study.Methods The Rheumatoid Arthritis Consortium International densely genotyped 186 autoimmune‐related regions in 3,339 anti‐CCP–negative RA patients and 15,870 controls across 6 different populations using the Illumina ImmunoChip array. We performed a case–control replication study of the anti‐CCP–negative markers with the strongest associations in that discovery study, in an independent cohort of anti‐CCP–negative UK RA patients. Individuals from the arcOGEN Consortium and Wellcome Trust Case Control Consortium were used as controls. Genotyping in cases was performed using Sequenom MassArray technology. Genome‐wide data from controls were imputed using the 1000 Genomes Phase I integrated variant call set release version 3 as a reference panel. Results After genotyping and imputation quality control procedures, data were available for 15 non‐HLA single‐nucleotide polymorphisms in 1,024 cases and 6,348 controls. We confirmed the known markers ANKRD55 (meta‐analysis odds ratio [OR] 0.80; P = 2.8 × 10−13) and BLK (OR 1.13; P = 7.0 × 10−6) and identified new and specific markers of anti‐CCP–negative RA (prolactin [PRL] [OR 1.13; P = 2.1 × 10−6] and NFIA [OR 0.85; P = 2.5 × 10−6]). Neither of these loci is associated with other common, complex autoimmune diseases. Conclusion Anti‐CCP–negative RA and anti‐CCP–positive RA are genetically different disease subsets that only partially share susceptibility factors. Genetic polymorphisms located near the PRL and NFIA genes represent examples of genetic susceptibility factors specific for anti‐CCP–negative RA.

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A Replication Study Confirms the Association of Dendritic Cell Immunoreceptor (DCIR) Polymorphisms with ACPA - Negative RA in a Large Asian Cohort

Cited by 22 publications

References 20 publications

Dendritic Cell Immunoreceptor Regulates Chikungunya Virus Pathogenesis in Mice

Dendritic Cell Immunoreceptor Regulates Chikungunya Virus Pathogenesis in Mice

C-type lectin receptor DCIR modulates immunity to tuberculosis by sustaining type I interferon signaling in dendritic cells

Replication of Associations of Genetic Loci Outside the HLA Region With Susceptibility to Anti–Cyclic Citrullinated Peptide–Negative Rheumatoid Arthritis

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