Interleukin-7 induced immunopathology in arthritis

Hartgring, Sarita A. Y.; Bijlsma, J. W. J.; Lafeber, F.P.; Roon, Joël A G van

doi:10.1136/ard.2006.058479

Cited by 66 publications

(62 citation statements)

References 64 publications

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“…IL-7 is a potent pro-inflammatory cytokine, known for its critical role in T-cell development and survival and its role in B-cell development. 40 MIP-1b is a chemokine, which is crucial in recruiting macrophages and other pro-inflammatory cells. 41 Although the function of these adipokines on adipose tissue is still poorly documented, both may have a role in initiating and shaping the immune-inflammatory responses in this tissue.…”

Section: Discussionmentioning

confidence: 99%

Endocannabinoids regulate adipokine production and the immune balance of omental adipose tissue in human obesity

Ge¹,

Maury²,

Rycken³

et al. 2012

Int J Obes

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OBJECTIVES: (1) To investigate whether modulation of the cannabinoid type 1 receptor (CB1R) directly regulates the production of adiponectin (ApN) and other adipokines in omental adipose tissue (OAT) of obese subjects, (2) to establish in which cellular fraction of OAT the effects of CB1R blockade take place and (3) to unravel the underlying mechanisms. SUBJECTS AND METHODS: OAT was obtained from 30 obese subjects (body mass index: 40.6±1.3 kg m À 2 ) undergoing abdominal surgery. Primary cultures of explants or of freshly isolated adipocytes or stromal-vascular cells (SVCs) were used. RESULTS: In OAT explants, the CB1R blocker Rimonabant upregulated ApN gene expression. mRNA abundance of omentin that exhibits insulin-sensitizing properties was upregulated as well. Conversely, mRNA levels of two pro-inflammatory cytokines, macrophage inflammatory protein (MIP)-1b and interleukin (IL)-7 were downregulated. We next examined where these effects took place within OAT. CB1R expression was similar in both cellular fractions. In isolated mature adipocytes, blockade of CB1R reproduced the increase of ApN mRNA and the decrease of IL-7 mRNA, while inducing a rise of ApN secretion into the medium. In isolated SVC, gene expression of omentin, which is restricted to this fraction, was augmented, while that of MIP-1b was diminished. Finally, we deciphered the mechanisms leading to ApN regulation by the endocannabinoid system (ES). We first established that ApN regulation was actually mediated by the CB1R: ApN gene expression was upregulated by Rimonabant and downregulated by the CB1R agonist arachidonyl-2-chloroethylamide (ACEA). Upregulation of ApN by Rimonabant was unaltered by inhibiting cAMP production. However, downregulation of ApN by ACEA was fully reversed by an inhibitor of p38 mitogen-activated protein kinase (p38MAPK) and ACEA increased p38MAPK phosphorylation. CONCLUSIONS: Blockade of CB1R attenuates the inflammatory state in both cellular fractions of OAT either by increasing ApN and omentin production or by decreasing mRNAs of MIP-1b and IL-7. ApN regulation by the ES partly involves p38MAPK.

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Section: Discussionmentioning

confidence: 99%

Endocannabinoids regulate adipokine production and the immune balance of omental adipose tissue in human obesity

Ge¹,

Maury²,

Rycken³

et al. 2012

Int J Obes

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“…In vivo, LTi cells develop from BM precursors relatively inefficiently unless exogenous IL-7 is provided. Considering the role of LTi cells in normal and ectopic lymphoid tissue development (9), adult LTi cells may play an important role in chronic inflammatory diseases such as rheumatoid arthritis, where local IL-7 availability is increased (26).…”

Section: Table I Surface Expression Profile Of Fetal and Adult Lti Cmentioning

confidence: 99%

Cutting Edge: IL-7 Regulates the Peripheral Pool of Adult RORγ+ Lymphoid Tissue Inducer Cells

Schmutz¹,

Bosco

Chappaz³

et al. 2009

The Journal of Immunology

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During fetal life, CD4+CD3− lymphoid tissue inducer (LTi) cells are required for lymph node and Peyer’s patch development in mice. In adult animals, CD4+CD3− cells are found in low numbers in lymphoid organs. Whether adult CD4+CD3− cells are LTi cells and are generated and maintained through cytokine signals has not been directly addressed. In this study we show that adult CD4+CD3− cells adoptively transferred into neonatal CXCR5−/− mice induced the formation of intestinal lymphoid tissues, demonstrating for the first time their bona fide LTi function. Increasing IL-7 availability in wild-type mice either by IL-7 transgene expression or treatment with IL-7/anti-IL-7 complexes increased adult LTi cell numbers through de novo generation from bone marrow cells and increased the survival and proliferation of LTi cells. Our observations demonstrate that adult CD4+lineage− cells are LTi cells and that the availability of IL-7 determines the size of the adult LTi cell pool.

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“…Because LFA-1 plays important roles in many cellular processes, disorder of its functions can cause serious autoimmune and inflammatory diseases and is implicated in multiple cancers including myeloma, malignant lymphoma, and acute and chronic leukemias (21)(22)(23)(24)(25). Thus, it has become a therapeutic target for the treatment of multiple autoimmune and inflammatory diseases and cancers (8,26,27).…”

mentioning

confidence: 99%

Efalizumab binding to the LFA-1 α_LI domain blocks ICAM-1 binding via steric hindrance

Wang

Peng

et al. 2009

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

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Interleukin-7 induced immunopathology in arthritis

Cited by 66 publications

References 64 publications

Endocannabinoids regulate adipokine production and the immune balance of omental adipose tissue in human obesity

Endocannabinoids regulate adipokine production and the immune balance of omental adipose tissue in human obesity

Cutting Edge: IL-7 Regulates the Peripheral Pool of Adult RORγ+ Lymphoid Tissue Inducer Cells

Efalizumab binding to the LFA-1 α_LI domain blocks ICAM-1 binding via steric hindrance

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Interleukin-7 induced immunopathology in arthritis

Cited by 66 publications

References 64 publications

Endocannabinoids regulate adipokine production and the immune balance of omental adipose tissue in human obesity

Endocannabinoids regulate adipokine production and the immune balance of omental adipose tissue in human obesity

Cutting Edge: IL-7 Regulates the Peripheral Pool of Adult RORγ+ Lymphoid Tissue Inducer Cells

Efalizumab binding to the LFA-1 αLI domain blocks ICAM-1 binding via steric hindrance

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Efalizumab binding to the LFA-1 α_LI domain blocks ICAM-1 binding via steric hindrance