Nonoverlapping Expression of IL10, IL12p40, and IFNγ mRNA in the Marginal Zone and T Cell Zone of the Spleen after Antigenic Stimulation

Kalies, Kathrin; König, Peter; Zhang, Yongming; Deierling, Maria; Barthelmann, Julia; Stamm, Claudia; Westermann, Juergen

doi:10.4049/jimmunol.180.8.5457

Cited by 16 publications

(14 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it is also possible that this approach influenced the milieu in the infected skin, thereby modulating the disease outcome. Therefore, in the present study, we used the combination of laser microdissection and real-time RT-PCR to analyze the expression of the Th1/Th2 cytokines quantitatively with high specificity and sensitivity in vivo [20,21]. To do this, we focused on the TCZ and the T/B border because especially at these sites cytokines are produced, which have an impact on T-cell activation (Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The protective Th1 response in mice is induced in the T-cell zone only three weeks after infection with Leishmania major and not during early T-cell activation

Barthelmann

Nietsch

Blessenohl

et al. 2011

Med Microbiol Immunol

Self Cite

View full text Add to dashboard Cite

The protozoan parasite Leishmania spp. causes clinical pictures ranging in severity from spontaneously healing skin ulcers to systemic disease. The immune response associated with healing involves the differentiation of IFNγ-producing Th1 cells, whereas the non-healing phenotype is associated with IL4-producing Th2 cells. The widespread assumption has been that the T-cell differentiation that leads to a healing or non-healing phenotype is established at the time of T-cell activation early after infection. By selectively analyzing the expression of cytokine genes in the T-cell zones of lymph nodes of resistant (Th1) C57BL/6 mice and susceptible (Th2) BALB/c mice during an infection with Leishmania major in vivo, we show that the early T-cell response does not differ between C57BL/6 mice and BALB/c mice. Instead, Th1/Th2 polarization appears suddenly 3 weeks after infection. At the same time point, the number of parasites increases in lymph nodes of both mouse strains, but about 100-fold more in susceptible BALB/c mice. We conclude that the protective Th1 response in C57BL/6 mice is facilitated by the capacity of their innate effector cells to keep parasite numbers at low levels.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The same batch of cDNA (20 ll) was used to determine the cycles of threshold (ct) of the cytokine genes. The amount of cDNA copies was normalized to the housekeeping gene, metastatic lymph node gene 51 (MLN51), as described [20,21].…”

Section: Histological Analysismentioning

confidence: 99%

The protective Th1 response in mice is induced in the T-cell zone only three weeks after infection with Leishmania major and not during early T-cell activation

Barthelmann

Nietsch

Blessenohl

et al. 2011

Med Microbiol Immunol

Self Cite

View full text Add to dashboard Cite

show abstract

“…RT-PCR of mouse skin was performed as described (19) using the following sets of primers: MLN51 forward (59-CCAAGCCAGCCTTCATTCTTG-39) and MLN51 reverse (59-TAACGCTTAGCTCGACCACTCTG-39) and IL-1b forward (59-CTTCCAGGATGAGGACATGAG-39) and IL-1b reverse (59-CACAC-CAGCAGGTTATCATC-39).…”

Section: Rt-pcrmentioning

confidence: 99%

Caspase-1–Independent IL-1 Release Mediates Blister Formation in Autoantibody-Induced Tissue Injury through Modulation of Endothelial Adhesion Molecules

Sadeghi

Lockmann

Hund

et al. 2015

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Although reports documented aberrant cytokine expression in autoimmune bullous dermatoses (AIBDs), cytokine-targeting therapies have not been established in these disorders. We showed previously that IL-6 treatment protected against tissue destruction in experimental epidermolysis bullosa acquisita (EBA), an AIBD caused by autoantibodies to type VII collagen (COL7). The anti-inflammatory effects of IL-6 were mediated by induction of IL-1ra, and prophylactic IL-1ra administration prevented blistering. In this article, we demonstrate elevated serum concentrations of IL-1β in both mice with experimental EBA induced by injection of anti-COL7 IgG and in EBA patients. Increased IL-1α and IL-1β expression also was observed in the skin of anti-COL7 IgG-injected wild-type mice compared with the significantly less diseased IL-1R–deficient or wild-type mice treated with the IL-1R antagonist anakinra or anti–IL-1β. These findings suggested that IL-1 contributed to recruitment of inflammatory cells into the skin. Accordingly, the expression of ICAM-1 was decreased in IL-1R–deficient and anakinra-treated mice injected with anti-COL7. This effect appeared to be specifically attributable to IL-1 because anakinra blocked the upregulation of different endothelial adhesion molecules on IL-1–stimulated, but not on TNF-α–stimulated, cultured endothelial cells. Interestingly, injection of caspase-1/11–deficient mice with anti-COL7 IgG led to the same extent of skin lesions as in wild-type mice. Collectively, our data suggest that IL-1, independently of caspase-1, contributes to the pathogenesis of EBA. Because anti–IL-1β in a prophylactic setting and anakinra in a quasi-therapeutic setting (i.e., when skin lesions had already developed) improved experimental EBA, IL-1 appears to be a potential therapeutic target for EBA and related AIBDs.

show abstract

“…Analysis of cytokine gene expression was performed, as detailed elsewhere (23,24). In brief, RNA was extracted from cryosections of whole lymph nodes or peripheral blood cells using the innuPREP RNA Mini Kit (Analytik Jena, Jena, Germany).…”

Section: Rna Isolation Cdna Synthesis and Quantitative Real-time Pcrmentioning

confidence: 99%

Complement-Fixing Anti-Type VII Collagen Antibodies Are Induced in Th1-Polarized Lymph Nodes of Epidermolysis Bullosa Acquisita-Susceptible Mice

Hammers

Bieber

Kalies

et al. 2011

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

The environment encountered in secondary lymphoid organs (e.g., lymph nodes) influences the outcome of immune responses. Immunization of mice with type VII collagen, an adhesion protein expressed at the cutaneous basement membrane, induces experimental epidermolysis bullosa acquisita (EBA). In this model, clinical disease is associated with the H2s haplotype of the MHC found in SJL/J mice. Most other strains (e.g., BALB/c, C57BL/6, NZM2410/J) are resistant to clinical disease, despite autoantibody production. Comparison of autoantibody response in EBA-resistant and -susceptible mice showed an IgG2-dominated response in the latter. We hypothesized that EBA susceptibility is due to specific cytokine gene expression in draining lymph nodes (dLN). To challenge this hypothesis, EBA-susceptible (SJL/J) and -resistant (BALB/c, C57BL/6) mice were immunized with type VII collagen, followed by analysis of clinical phenotype, subclasses of circulating and tissue-bound autoantibodies, complement activation, and cytokine gene expression in dLN. Disease manifestation was associated with induction of complement-fixing autoantibodies, confirming previous observations. Furthermore, however, IFN-γ/IL-4 ratio in dLN of EBA-susceptible mice was significantly increased compared with EBA-resistant strains, suggesting a Th1 polarization. Immunization of H2s-congenic C57BL/6 mice (B6.SJL-H2s) led to Th1 polarization in dLN and clinical disease. In addition to their cytokine milieu, EBA-susceptible and -resistant mice also differed regarding the expression of FcγR on peripheral leukocytes, in which a higher FcγRIV expression in SJL/J and B6.SJL-H2s mice, compared with C57BL/6, was associated with skin lesions. In summary, blistering in experimental EBA is regulated by both adaptive (divergent class switch recombination due to polarized cytokine expression) and innate (FcγR expression) immune mechanisms.

show abstract

Nonoverlapping Expression of IL10, IL12p40, and IFNγ mRNA in the Marginal Zone and T Cell Zone of the Spleen after Antigenic Stimulation

Cited by 16 publications

References 51 publications

The protective Th1 response in mice is induced in the T-cell zone only three weeks after infection with Leishmania major and not during early T-cell activation

The protective Th1 response in mice is induced in the T-cell zone only three weeks after infection with Leishmania major and not during early T-cell activation

Caspase-1–Independent IL-1 Release Mediates Blister Formation in Autoantibody-Induced Tissue Injury through Modulation of Endothelial Adhesion Molecules

Complement-Fixing Anti-Type VII Collagen Antibodies Are Induced in Th1-Polarized Lymph Nodes of Epidermolysis Bullosa Acquisita-Susceptible Mice

Contact Info

Product

Resources

About