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Regulation of inflammatory responses by IL-17F.

Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, Wang YH, Schluns KS, Broaddus RR, Zhu Z, Dong C - J. Exp. Med. (2008)

Bottom Line: IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis.In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease.Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.

ABSTRACT
Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor-associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F-deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases.

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Analysis of T and B cell responses in IL-17 and IL-17F KO animals. IL-17F KO, IL-17 KO, and WT control mice were immunized with KLH in CFA (three per group). 7 d later, the mice were killed and spleens and blood were collect. (A) Splenocytes from the immunized mice were restimulated with KLH for 3 d, and cytokine expression was measured by ELISA. (B) KLH-specific antibodies were measured in the sera by ELISA. The sera were subject to a threefold serial dilution, and the antibody concentrations are shown as the mean for each group. Results are mean ± SD.
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fig4: Analysis of T and B cell responses in IL-17 and IL-17F KO animals. IL-17F KO, IL-17 KO, and WT control mice were immunized with KLH in CFA (three per group). 7 d later, the mice were killed and spleens and blood were collect. (A) Splenocytes from the immunized mice were restimulated with KLH for 3 d, and cytokine expression was measured by ELISA. (B) KLH-specific antibodies were measured in the sera by ELISA. The sera were subject to a threefold serial dilution, and the antibody concentrations are shown as the mean for each group. Results are mean ± SD.

Mentions: As a first step to analyze these animals, IL-17F KO, IL-17 KO, and WT control mice were immunized with KLH in CFA. 7 d after immunization, the animals were killed and spleens were collected and restimulated with KLH. In ELISA analysis, IL-17F and IL-17 could not be detected in IL-17F KO and IL-17 KO splenocyte cultures, respectively (Fig. 4 A). Intracellular cytokine staining also revealed no IL-17 and IL-17F expression in the corresponding animals (Fig. S1 B). Levels of IL-17F were also reduced in IL-17 KO cells, whereas IL-17F deficiency did not lead to a substantial reduction of IL-17 expression (Fig. 4 A). IL-22 expression levels were moderately reduced in both IL-17F KO and IL-17 KO samples (Fig. 4 A). In addition to T cell responses, KLH-specific Ig levels in sera from immunized IL-17F KO, IL-17 KO, and WT mice were determined by ELISA (Fig. 4 B). Compared with WT mice, IL-17–deficient mice exhibited lower levels of IgM, total IgG, and all IgG subclasses tested, consistent with a previous paper on 2,4,6-trinitrochlorobenzene–challenged IL-17–deficient mice (33), whereas IL-17F deficiency resulted in a significant increase of IgG2a levels, though IFN-γ levels were not increased in these mice. These data suggest that IL-17F and IL-17 play important but perhaps differential roles in humoral immunity.


Regulation of inflammatory responses by IL-17F.

Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, Wang YH, Schluns KS, Broaddus RR, Zhu Z, Dong C - J. Exp. Med. (2008)

Analysis of T and B cell responses in IL-17 and IL-17F KO animals. IL-17F KO, IL-17 KO, and WT control mice were immunized with KLH in CFA (three per group). 7 d later, the mice were killed and spleens and blood were collect. (A) Splenocytes from the immunized mice were restimulated with KLH for 3 d, and cytokine expression was measured by ELISA. (B) KLH-specific antibodies were measured in the sera by ELISA. The sera were subject to a threefold serial dilution, and the antibody concentrations are shown as the mean for each group. Results are mean ± SD.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2373839&req=5

fig4: Analysis of T and B cell responses in IL-17 and IL-17F KO animals. IL-17F KO, IL-17 KO, and WT control mice were immunized with KLH in CFA (three per group). 7 d later, the mice were killed and spleens and blood were collect. (A) Splenocytes from the immunized mice were restimulated with KLH for 3 d, and cytokine expression was measured by ELISA. (B) KLH-specific antibodies were measured in the sera by ELISA. The sera were subject to a threefold serial dilution, and the antibody concentrations are shown as the mean for each group. Results are mean ± SD.
Mentions: As a first step to analyze these animals, IL-17F KO, IL-17 KO, and WT control mice were immunized with KLH in CFA. 7 d after immunization, the animals were killed and spleens were collected and restimulated with KLH. In ELISA analysis, IL-17F and IL-17 could not be detected in IL-17F KO and IL-17 KO splenocyte cultures, respectively (Fig. 4 A). Intracellular cytokine staining also revealed no IL-17 and IL-17F expression in the corresponding animals (Fig. S1 B). Levels of IL-17F were also reduced in IL-17 KO cells, whereas IL-17F deficiency did not lead to a substantial reduction of IL-17 expression (Fig. 4 A). IL-22 expression levels were moderately reduced in both IL-17F KO and IL-17 KO samples (Fig. 4 A). In addition to T cell responses, KLH-specific Ig levels in sera from immunized IL-17F KO, IL-17 KO, and WT mice were determined by ELISA (Fig. 4 B). Compared with WT mice, IL-17–deficient mice exhibited lower levels of IgM, total IgG, and all IgG subclasses tested, consistent with a previous paper on 2,4,6-trinitrochlorobenzene–challenged IL-17–deficient mice (33), whereas IL-17F deficiency resulted in a significant increase of IgG2a levels, though IFN-γ levels were not increased in these mice. These data suggest that IL-17F and IL-17 play important but perhaps differential roles in humoral immunity.

Bottom Line: IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis.In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease.Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.

ABSTRACT
Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor-associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F-deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases.

Show MeSH
Related in: MedlinePlus