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LPA Promotes T Cell Recruitment through Synthesis of CXCL13.

Hui W, Zhao C, Bourgoin SG - Mediators Inflamm. (2015)

Bottom Line: Here we report in a murine air pouch model of inflammation that LPA induced CXCL13 secretion in a time-dependent manner and with exacerbation of the response when LPA was administered after a pretreatment with TNF-α, a key inflammatory cytokine.CXCL13 neutralization using a blocking antibody injected into air pouches prior to administration of LPA into TNF-α-primed air pouches decreased CD3(+) cell influx.Our data highlight that LPA-mediated CXCL13 secretion plays a role in T cell recruitment and participates in regulation of the inflammatory response.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology and Immunology Research Center, CHU de Québec Research Center and Faculty of Medicine, Laval University, 2705 Laurier Boulevard, Québec, QC, Canada G1V 4G2.

ABSTRACT
Lysophosphatidic acid (LPA) is a bioactive phospholipid playing an important role in various inflammatory diseases by inducing expression and secretion of many inflammatory cytokines/chemokines. Here we report in a murine air pouch model of inflammation that LPA induced CXCL13 secretion in a time-dependent manner and with exacerbation of the response when LPA was administered after a pretreatment with TNF-α, a key inflammatory cytokine. LPA mediates recruitment of leukocytes, including that of CD3(+) cells into unprimed and TNF-α-primed air pouches. CXCL13 neutralization using a blocking antibody injected into air pouches prior to administration of LPA into TNF-α-primed air pouches decreased CD3(+) cell influx. Our data highlight that LPA-mediated CXCL13 secretion plays a role in T cell recruitment and participates in regulation of the inflammatory response.

No MeSH data available.


Related in: MedlinePlus

Effect of the CXCL13 neutralizing antibody on LPA-mediated lymphocyte recruitment into TNF-α-primed air pouches. Air pouch tissues were pretreated with TNF-α (50 ng) for 16 h prior to administration of LPA (3 μg). Where indicated, the anti-CXCL13 neutralizing antibody or the isotype control antibody (IgG2A, 10 μg) was administered into the air pouches 15 min prior to stimulation with LPA for 4 h. The absolute numbers of CD3+ T cells in air pouch lavage fluids were determined by flow cytometry as described in Section 2. Data are the mean ± SE of at least 5 mice/group. ∗∗P < 0.01 by analysis of variance.
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fig4: Effect of the CXCL13 neutralizing antibody on LPA-mediated lymphocyte recruitment into TNF-α-primed air pouches. Air pouch tissues were pretreated with TNF-α (50 ng) for 16 h prior to administration of LPA (3 μg). Where indicated, the anti-CXCL13 neutralizing antibody or the isotype control antibody (IgG2A, 10 μg) was administered into the air pouches 15 min prior to stimulation with LPA for 4 h. The absolute numbers of CD3+ T cells in air pouch lavage fluids were determined by flow cytometry as described in Section 2. Data are the mean ± SE of at least 5 mice/group. ∗∗P < 0.01 by analysis of variance.

Mentions: It was reported previously that antibody neutralization of CXCL13 can prevent migration of double-negative regulatory T lymphocytes to cardiac allografts implanted in the abdomen of mice [32]. To examine whether a correlation exists between CXCL13 secretion in response to LPA and CD3+ lymphocyte recruitment in our mouse model, a neutralizing anti-CXCL13 antibody was injected into TNF-α-primed air pouches prior to LPA stimulation. Injection of the neutralizing antibody against CXCL13 prior to LPA into the air pouch significantly reduced LPA-induced CD3+ lymphocyte recruitment into TNF-α-primed air pouches, whereas the isotype control antibody had no significant effect on LPA-mediated CD3+ lymphocyte influx (Figure 4). Taken together, the data indicate that CXCL13 plays a role in LPA-mediated recruitment of CD3+ lymphocytes into the air pouches.


LPA Promotes T Cell Recruitment through Synthesis of CXCL13.

Hui W, Zhao C, Bourgoin SG - Mediators Inflamm. (2015)

Effect of the CXCL13 neutralizing antibody on LPA-mediated lymphocyte recruitment into TNF-α-primed air pouches. Air pouch tissues were pretreated with TNF-α (50 ng) for 16 h prior to administration of LPA (3 μg). Where indicated, the anti-CXCL13 neutralizing antibody or the isotype control antibody (IgG2A, 10 μg) was administered into the air pouches 15 min prior to stimulation with LPA for 4 h. The absolute numbers of CD3+ T cells in air pouch lavage fluids were determined by flow cytometry as described in Section 2. Data are the mean ± SE of at least 5 mice/group. ∗∗P < 0.01 by analysis of variance.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4539179&req=5

fig4: Effect of the CXCL13 neutralizing antibody on LPA-mediated lymphocyte recruitment into TNF-α-primed air pouches. Air pouch tissues were pretreated with TNF-α (50 ng) for 16 h prior to administration of LPA (3 μg). Where indicated, the anti-CXCL13 neutralizing antibody or the isotype control antibody (IgG2A, 10 μg) was administered into the air pouches 15 min prior to stimulation with LPA for 4 h. The absolute numbers of CD3+ T cells in air pouch lavage fluids were determined by flow cytometry as described in Section 2. Data are the mean ± SE of at least 5 mice/group. ∗∗P < 0.01 by analysis of variance.
Mentions: It was reported previously that antibody neutralization of CXCL13 can prevent migration of double-negative regulatory T lymphocytes to cardiac allografts implanted in the abdomen of mice [32]. To examine whether a correlation exists between CXCL13 secretion in response to LPA and CD3+ lymphocyte recruitment in our mouse model, a neutralizing anti-CXCL13 antibody was injected into TNF-α-primed air pouches prior to LPA stimulation. Injection of the neutralizing antibody against CXCL13 prior to LPA into the air pouch significantly reduced LPA-induced CD3+ lymphocyte recruitment into TNF-α-primed air pouches, whereas the isotype control antibody had no significant effect on LPA-mediated CD3+ lymphocyte influx (Figure 4). Taken together, the data indicate that CXCL13 plays a role in LPA-mediated recruitment of CD3+ lymphocytes into the air pouches.

Bottom Line: Here we report in a murine air pouch model of inflammation that LPA induced CXCL13 secretion in a time-dependent manner and with exacerbation of the response when LPA was administered after a pretreatment with TNF-α, a key inflammatory cytokine.CXCL13 neutralization using a blocking antibody injected into air pouches prior to administration of LPA into TNF-α-primed air pouches decreased CD3(+) cell influx.Our data highlight that LPA-mediated CXCL13 secretion plays a role in T cell recruitment and participates in regulation of the inflammatory response.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology and Immunology Research Center, CHU de Québec Research Center and Faculty of Medicine, Laval University, 2705 Laurier Boulevard, Québec, QC, Canada G1V 4G2.

ABSTRACT
Lysophosphatidic acid (LPA) is a bioactive phospholipid playing an important role in various inflammatory diseases by inducing expression and secretion of many inflammatory cytokines/chemokines. Here we report in a murine air pouch model of inflammation that LPA induced CXCL13 secretion in a time-dependent manner and with exacerbation of the response when LPA was administered after a pretreatment with TNF-α, a key inflammatory cytokine. LPA mediates recruitment of leukocytes, including that of CD3(+) cells into unprimed and TNF-α-primed air pouches. CXCL13 neutralization using a blocking antibody injected into air pouches prior to administration of LPA into TNF-α-primed air pouches decreased CD3(+) cell influx. Our data highlight that LPA-mediated CXCL13 secretion plays a role in T cell recruitment and participates in regulation of the inflammatory response.

No MeSH data available.


Related in: MedlinePlus