Natural killer cell and gamma delta T cell alterations in enthesitis related arthritis category of juvenile idiopathic arthritis

Gaur, Priyanka; Misra, Ramnath; Aggarwal, Amita

doi:10.1016/j.clim.2015.07.012

Cited by 32 publications

(19 citation statements)

References 37 publications

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“…IL‐23 acts on CD4 cells, NK cells and gamma‐delta T cells and induces IL‐17 production. We have recently shown an increased frequency of IL‐17‐producing CD4, NK and gamma‐delta T cells in patients with JIA‐ERA .…”

Section: Discussionmentioning

confidence: 98%

Intermediate monocytes are increased in enthesitis-related arthritis, a category of juvenile idiopathic arthritis

Gaur

Myles

Misra

et al. 2016

Clinical and Experimental Immunology

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Microarray of peripheral blood (PB) and synovial fluid mononuclear cells (PBMC, SFMC) of patients with juvenile idiopathic arthritis-enthesitis-related arthritis (JIA-ERA) has shown the involvement of monocytes. On the basis of CD14 and CD16 expression, monocytes are classified as classical, intermediate and non-classical. In response to Toll-like receptor (TLR) stimulation, intermediate monocytes produce proinflammatory cytokines and play a role in inflammatory diseases. Therefore, we have studied the microarray profile of monocytes, the frequency of their subsets and cytokine production. Monocyte-specific microarray analysis was performed in six healthy controls' PBMC and six patients' PBMC and SFMC using Illumina chips WG12. Monocyte subsets were assessed in 46 patients with JIA-ERA and 17 healthy controls and 17 disease controls by flow cytometry. Interleukin (IL)-23 and tumour necrosis factor (TNF) levels were measured in culture supernatants of eight controls and seven patients' PBMC/SFMC with/without lipopolysaccharide (LPS) stimulation. Cytokine-producing intermediate monocytes were assessed by flow cytometry. Genes related to antigen presentation, cytokine signalling and TLR pathway were regulated differentially in PB and synovial monocytes of patients with JIA-ERA. Key genes of intermediate monocytes, such as CLEC10A and MARCO, were expressed three- to fourfold more in JIA-ERA. In PB, the frequency of intermediate monocytes was significantly higher in JIA-ERA (4·90% ± 3·5) compared to controls (1·8% ± 1·06; P < 0·001). Patients' synovial cells also had more intermediate monocytes compared to PB (11·25% ± 11·32, 5·9% ± 4·8; P = 0.004). Intermediate monocytes are the major producers of IL-23. Thus, intermediate monocytes may play an important role in JIA-ERA, possibly by producing cytokines, and contribute to joint inflammation.

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Section: Discussionmentioning

confidence: 98%

Intermediate monocytes are increased in enthesitis-related arthritis, a category of juvenile idiopathic arthritis

Gaur

Myles

Misra

et al. 2016

Clinical and Experimental Immunology

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“…So far, only a few studies have analyzed γ/δ T cells in SpA patients. Two recent studies showed an enrichment of IL‐17−producing or even IL‐23R+ IL‐17−producing γ/δ T cells within the peripheral blood of patients with enthesitis‐related arthritis or AS , respectively. The presence of γ/δ T cells within the inflamed synovia of patients with RA or juvenile idiopathic arthritis has also been observed, although data about their pathogenic potential were a subject of controversy .…”

Section: Discussionmentioning

confidence: 99%

“…In fact, elevated levels of serum IL‐17 and IL‐17– and IL‐22–producing peripheral blood CD4+ T cells have been observed in AS patients . Notably, patients with enthesitis‐related arthritis also displayed increased frequencies of synovial fluid IL‐17 .…”

mentioning

confidence: 99%

“…Therefore, in this study we hypothesized and investigated to what extent γ/δ T cells constituted the entheseal lymphocyte population. In humans, an enrichment of IL‐17−producing IL‐23R+ γ/δ T cells was recently identified in the peripheral blood of patients with AS or enthesitis‐related arthritis . Thus, it was likely that γ/δ T cells are enthesis‐resident key producers of IL‐17A.…”

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confidence: 99%

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Interleukin‐23–Dependent γ/δ T Cells Produce Interleukin‐17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice

Reinhardt

Yevsa

Worbs

et al. 2016

Arthritis & Rheumatology

187

130

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Objective. The spondyloarthritides (SpA) are a group of rheumatic diseases characterized by ossification and inflammation of entheseal tissue, the region where tendon attaches to bone. Interleukin-23 (IL-23) is involved in the pathogenesis of SpA by acting on IL-23 receptor (IL-23R) expressed on enthesis-resident lymphocytes. Upon IL-23 binding, CD31CD42CD82 tissueresident lymphocytes secrete IL-17A and IL-22, leading to inflammation, bone loss, and ossification. Knowledge about enthesis-resident lymphocytes remains fragmentary, and the contribution of entheseal g/d T cells in particular is not clear. This study was undertaken to investigate the presence of g/d T cells in the enthesis.Methods. We used 2-photon microscopy and flow cytometry to analyze entheseal lymphocytes from C57BL/ 6, Tcrd-H2BeGFP, Rorc-GFP, and IL-23R-eGFP mice. To analyze entheseal g/d T cells in IL-232induced inflammation, Tcrd-H2BeGFP mice were crossed with mice of the susceptible B10.RIII background. Hydrodynamic injection of IL-23 minicircle DNA was performed for overexpression of IL-23 and induction of inflammation. Light-sheet fluorescence microscopy was used to visualize arthritic inflammation.

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“…In addition, g/d T cell numbers decrease after the infusion and were found to be lower than before zoledronic acid treatment, even at 12-month follow-up (8). This effect on circulating lymphocytes may be attributed to the activation, differentiation, and homing of these cells at tissue levels (9). Akitsu et al have found increased homing of g/d T cells in mice with inflammatory arthritis (10).…”

Section: Could G/d T Cells Explain Adverse Effects Of Zoledronic Acidmentioning

confidence: 99%

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Reinhardt

Prinz

2017

Arthritis & Rheumatology

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Natural killer cell and gamma delta T cell alterations in enthesitis related arthritis category of juvenile idiopathic arthritis

Cited by 32 publications

References 37 publications

Intermediate monocytes are increased in enthesitis-related arthritis, a category of juvenile idiopathic arthritis

Intermediate monocytes are increased in enthesitis-related arthritis, a category of juvenile idiopathic arthritis

Interleukin‐23–Dependent γ/δ T Cells Produce Interleukin‐17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice

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