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Overexpression of CIITA in T cells aggravates Th2-mediated colitis in mice.

Kim TW, Park HJ, Choi EY, Jung KC - J. Korean Med. Sci. (2006)

Bottom Line: The MHC class II transactivator (CIITA) is the master transcriptional regulator of genes involved in MHC class II restricted antigen presentation.Previously we suggested another role of CIITA in Th1/Th2 balance by demonstrating that forced expression of CIITA in murine T cells repressed Th1 immunity both in vitro and in vivo.And, CD4+ T cells from the mesenteric lymph node of CIITA-transgenic mice treated with oxazolone exhibited a high level of IL-4 secretion.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Hallym University College of Medicine, Chuncheon, Korea.

ABSTRACT
The MHC class II transactivator (CIITA) is the master transcriptional regulator of genes involved in MHC class II restricted antigen presentation. Previously we suggested another role of CIITA in Th1/Th2 balance by demonstrating that forced expression of CIITA in murine T cells repressed Th1 immunity both in vitro and in vivo. However, the results were contradictory to the report that CIITA functioned to suppress the production of Th2 cytokine by CD4+ T cells in CIITA deficient mice. In this study, we investigated the influence of constitutive expression of CIITA in T cells on Th2 immune response in vivo using murine experimental colitis model. In the dextran sodium sulfate-induced acute colitis, a disease involving innate immunity, CIITA transgenic mice and wild type control mice showed similar progression of the disease. However, the development of oxazolone-induced colitis, a colitis mediated by predominantly Th2 immune response, was aggravated in CIITA-transgenic mice. And, CD4+ T cells from the mesenteric lymph node of CIITA-transgenic mice treated with oxazolone exhibited a high level of IL-4 secretion. Together, these data demonstrate that constitutive expression of CIITA in T cells skews immune response to Th2, resulting in aggravation of Th2-mediated colitis in vivo.

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Overexpression of CIITA expression in T cells did not affect DSS-mediated colitis. Wild type (WT) and CIITA-transgenic (Tg) mice were treated with 2.5% DSS for 7 days and body weight was monitored every day. DSS significantly reduced body weight for 7 days; this decrease in body weight was not affected by CIITA expression in T cells. Each point represents average weight data. The standard errors are indicated.
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Figure 1: Overexpression of CIITA expression in T cells did not affect DSS-mediated colitis. Wild type (WT) and CIITA-transgenic (Tg) mice were treated with 2.5% DSS for 7 days and body weight was monitored every day. DSS significantly reduced body weight for 7 days; this decrease in body weight was not affected by CIITA expression in T cells. Each point represents average weight data. The standard errors are indicated.

Mentions: Administration of DSS dissolved in water to mice induces acute colitis that occurs while the DSS is administered, and chronic colitis a little time after the administration (17). First, we investigated the effect of CIITA expression in T cells on the course of development of DSS-induced acute colitis. The average weights of the C57BL/6 wild type mice and CIITA-Tg mice on day 0 rights before the DSS administration were 22.9±1.4 g and 23.6±0.9 g, respectively. Then body weight was monitored for following 7 days, and histopathologic features were evaluated with tissue samples on day 7. Clinical symptoms of acute colitis such as a progressive loss of body weight (32.72±0.02% decreases compared with control group treated with water), hematochezia, and diarrhea were noted in the DSS-administered mice; loose stool was detected from day 4 and diarrhea and hematochezia were noted after the 5th day following administration of 2.5% DSS. CIITA-Tg mice showed similar pathway of acute colitis development after DSS administration and the extent of loss of body weight was comparable with that observed in normal mice treated with DSS (Fig. 1). Histopathologic examination of the colon on day 7 after DSS administration showed massive infiltration of mixed inflammatory cells in mucosa and submucosa with epithelial denudation, destruction of crypt architecture, and ulceration (Fig. 2). Pathologic changes in colon induced by DSS administration for 7 days were similar in wild type and CIITA Tg mice (Fig. 2), implying that CIITA expression in T cells did not influence the development of DSS-induced colitis.


Overexpression of CIITA in T cells aggravates Th2-mediated colitis in mice.

Kim TW, Park HJ, Choi EY, Jung KC - J. Korean Med. Sci. (2006)

Overexpression of CIITA expression in T cells did not affect DSS-mediated colitis. Wild type (WT) and CIITA-transgenic (Tg) mice were treated with 2.5% DSS for 7 days and body weight was monitored every day. DSS significantly reduced body weight for 7 days; this decrease in body weight was not affected by CIITA expression in T cells. Each point represents average weight data. The standard errors are indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2721999&req=5

Figure 1: Overexpression of CIITA expression in T cells did not affect DSS-mediated colitis. Wild type (WT) and CIITA-transgenic (Tg) mice were treated with 2.5% DSS for 7 days and body weight was monitored every day. DSS significantly reduced body weight for 7 days; this decrease in body weight was not affected by CIITA expression in T cells. Each point represents average weight data. The standard errors are indicated.
Mentions: Administration of DSS dissolved in water to mice induces acute colitis that occurs while the DSS is administered, and chronic colitis a little time after the administration (17). First, we investigated the effect of CIITA expression in T cells on the course of development of DSS-induced acute colitis. The average weights of the C57BL/6 wild type mice and CIITA-Tg mice on day 0 rights before the DSS administration were 22.9±1.4 g and 23.6±0.9 g, respectively. Then body weight was monitored for following 7 days, and histopathologic features were evaluated with tissue samples on day 7. Clinical symptoms of acute colitis such as a progressive loss of body weight (32.72±0.02% decreases compared with control group treated with water), hematochezia, and diarrhea were noted in the DSS-administered mice; loose stool was detected from day 4 and diarrhea and hematochezia were noted after the 5th day following administration of 2.5% DSS. CIITA-Tg mice showed similar pathway of acute colitis development after DSS administration and the extent of loss of body weight was comparable with that observed in normal mice treated with DSS (Fig. 1). Histopathologic examination of the colon on day 7 after DSS administration showed massive infiltration of mixed inflammatory cells in mucosa and submucosa with epithelial denudation, destruction of crypt architecture, and ulceration (Fig. 2). Pathologic changes in colon induced by DSS administration for 7 days were similar in wild type and CIITA Tg mice (Fig. 2), implying that CIITA expression in T cells did not influence the development of DSS-induced colitis.

Bottom Line: The MHC class II transactivator (CIITA) is the master transcriptional regulator of genes involved in MHC class II restricted antigen presentation.Previously we suggested another role of CIITA in Th1/Th2 balance by demonstrating that forced expression of CIITA in murine T cells repressed Th1 immunity both in vitro and in vivo.And, CD4+ T cells from the mesenteric lymph node of CIITA-transgenic mice treated with oxazolone exhibited a high level of IL-4 secretion.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Hallym University College of Medicine, Chuncheon, Korea.

ABSTRACT
The MHC class II transactivator (CIITA) is the master transcriptional regulator of genes involved in MHC class II restricted antigen presentation. Previously we suggested another role of CIITA in Th1/Th2 balance by demonstrating that forced expression of CIITA in murine T cells repressed Th1 immunity both in vitro and in vivo. However, the results were contradictory to the report that CIITA functioned to suppress the production of Th2 cytokine by CD4+ T cells in CIITA deficient mice. In this study, we investigated the influence of constitutive expression of CIITA in T cells on Th2 immune response in vivo using murine experimental colitis model. In the dextran sodium sulfate-induced acute colitis, a disease involving innate immunity, CIITA transgenic mice and wild type control mice showed similar progression of the disease. However, the development of oxazolone-induced colitis, a colitis mediated by predominantly Th2 immune response, was aggravated in CIITA-transgenic mice. And, CD4+ T cells from the mesenteric lymph node of CIITA-transgenic mice treated with oxazolone exhibited a high level of IL-4 secretion. Together, these data demonstrate that constitutive expression of CIITA in T cells skews immune response to Th2, resulting in aggravation of Th2-mediated colitis in vivo.

Show MeSH
Related in: MedlinePlus