Elevated expression of interleukin‐7 receptor in inflamed joints mediates interleukin‐7–induced immune activation in rheumatoid arthritis

Hartgring, Sarita A. Y.; Roon, Joël A G van; Wijk, Marion Wenting-van; Jacobs, Kim M. G.; Jahangier, Z. N.; Willis, Cynthia R.; Bijlsma, J. W. J.; Lafeber, Floris P. J. G.

doi:10.1002/art.24754

Cited by 70 publications

(58 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By microarray analysis, we identified the IL-7R gene as one of the most highly altered genes in RA synovial fluid macrophages (5-fold increase compared with normal macrophages; P ϭ 1.10 ϫ 10 Ϫ8 ). Other investigators using microarray analysis demonstrated a 4.7-fold increase in the expression of IL7R in the synovial tissue of patients with RA compared with that in the synovial tissue of patients with systemic lupus erythematosus or osteoarthritis (1), which is also consistent with the findings reported by Hartgring et al (2). Because macrophages in the synovial fluid originate from RA synovial tissue, expression of IL-7R was determined in RA compared with normal synovial tissue.…”

Section: To the Editorsupporting

confidence: 84%

“…We read with interest the report by Pickens et al (1), in which they documented increased expression of interleukin-7 (IL-7) and IL-7 receptor (IL-7R␣) in the synovial tissue of patients with rheumatoid arthritis (RA), thereby supporting the findings of previous studies (2,3). In addition, they demonstrated increased coexpression of IL-7 and IL-7R␣ in the circulating monocytes, synovial fluid macrophages, endothelial cells, and fibroblasts of patients with RA compared with healthy control subjects.…”

Section: To the Editorsupporting

confidence: 77%

See 1 more Smart Citation

Intraarticular soluble interleukin‐17 receptor levels are increased in patients with rheumatoid arthritis and correlate with local mediators of inflammation: Comment on the article by Pickens et al

Moret¹,

Badot²,

Lauwerys³

et al. 2012

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

Section: To the Editorsupporting

confidence: 84%

Section: To the Editorsupporting

confidence: 77%

Intraarticular soluble interleukin‐17 receptor levels are increased in patients with rheumatoid arthritis and correlate with local mediators of inflammation: Comment on the article by Pickens et al

Moret¹,

Badot²,

Lauwerys³

et al. 2012

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

“…For example, IL-7Ra expression by lymphoid cells in the joint in rheumatoid arthritis patients is increased compared with osteoarthritis patients (49). Treatment response to methotrexate in rheumatoid arthritis patients correlated with decreased IL-7 serum level, but not with TNF-a levels (50).…”

Section: Discussionmentioning

confidence: 98%

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

Kreft

Verbraak

Wierenga‐Wolf

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

The IL-7Rα single nucleotide polymorphism rs6897932 is associated with an increased risk for multiple sclerosis (MS). IL-7Rα is a promising candidate to be involved in autoimmunity, because it regulates T cell homeostasis, proliferation, and antiapoptotic signaling. However, the exact underlying mechanisms in the pathogenesis of MS are poorly understood. We investigated whether CD4 and CD8 lymphocyte subsets differed in IL-7Rα expression and functionality in 78 MS patients compared with 59 healthy controls (HC). A significantly higher frequency of IL-7Rα+ CD8 effector memory (CD8EM) was found in MS. Moreover, IL-7Rα membrane expression was significantly increased in MS in naive and memory CD8 (all p < 0.05) with a similar trend in CD8EM (p = 0.055). No correlation was found between the expression level or frequency of IL-7Rα+CD8+ and rs6897932 risk allele carriership. Upon IL-7 stimulation, MS patients had stronger STAT5 activation in CD8EM compared with HC. IL-7 stimulation had a differential effect on both mRNA and protein expression of granzyme A and granzyme B between MS and HC. Stainings of different lesions in postmortem MS brain material showed expression of IL-7 and CD8+IL-7Rα+ in preactive, but not in active, demyelinating MS lesions, indicating involvement of IL-7Rα+ lymphocytes in lesion development. The intralesional production of IL-7 in combination with the lower threshold for IL-7–induced cytotoxicity in MS may enhance the pathogenicity of these CD8 T cells. This is of special interest in light of the established demyelinating and cytotoxic actions of granzyme A.

show abstract

“…Another interpretation of the different findings in Caucasians and Africans could be that our initial findings in the Caucasian cohort may not have been related to levels of sIL-7Ra but could have been due to other SNPs in LD with rs6897932, which may have had an influence on CD4 T-cell recovery. This is of course possible but we believe this is less likely given the clear relationship in vitro between sIL-7Ra levels and IL-7 function in primary T-cells, 36,37 and that sIL-7Ra has a binding affinity similar to membrane-bound IL-7Ra on T-cells. 38 Finding the opposite association between genotype and phenotype in replicate genetic studies has been described previously as a 'flip-flop phenomenon,' 39 and is commonly reported in genetic association studies across different ethnic groups.…”

Section: Discussionmentioning

confidence: 99%

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

et al. 2011

View full text Add to dashboard Cite

We previously found an association between faster CD4 þ T-cell recovery in HIV-infected patients receiving combination antiretroviral therapy (cART) and interleukin-7 receptor-a (IL-7Ra) haplotype-2 in a predominantly Caucasian cohort. This study aims to determine whether this association was also significant in Africans. Patients were recruited from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort (n ¼ 352). We used survival analysis and linear mixed modelling (LMM) to determine factors associated with CD4 T-cell recovery. Eight IL-7Ra single-nucleotide polymorphisms (SNPs) were genotyped in both Africans and Caucasians (n ¼ 57). Soluble (s)IL-7Ra levels were measured by ELISA. In UARTO, IL-7Ra haplotype-2 was associated with slower CD4 T-cell recovery following cART by using survival analysis (P ¼ 0.020) and no association was found with LMM (P ¼ 0.958). The tagging-SNP for IL-7Ra haplotype-2 (rs6897932) was associated with decreased sIL-7Ra (Po0.001). The haplotypes for the IL-7Ra were significantly different in Africans and Caucasians. Using IL-7Ra genotypes we found slower CD4 T-cell recovery in UARTO patients was still associated with rs6897932 (P ¼ 0.009) and rs3194051 was associated with faster CD4 T-cell recovery (P ¼ 0.006). Unlike Caucasians, we did not demonstrate a significant association between IL-7Ra haplotype 2 and faster CD4 T-cell recovery in Africans. The IL-7Ra SNPs associated with CD4 T-cell recovery following cART differ in African and Caucasian cohorts.

show abstract

Elevated expression of interleukin‐7 receptor in inflamed joints mediates interleukin‐7–induced immune activation in rheumatoid arthritis

Cited by 70 publications

References 38 publications

Intraarticular soluble interleukin‐17 receptor levels are increased in patients with rheumatoid arthritis and correlate with local mediators of inflammation: Comment on the article by Pickens et al

Intraarticular soluble interleukin‐17 receptor levels are increased in patients with rheumatoid arthritis and correlate with local mediators of inflammation: Comment on the article by Pickens et al

The IL-7Rα Pathway Is Quantitatively and Functionally Altered in CD8 T Cells in Multiple Sclerosis

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

Contact Info

Product

Resources

About