A pivotal role of Rho GTPase in the regulation of morphology and function of dendritic cells.

نویسندگان

  • M Kobayashi
  • E Azuma
  • M Ido
  • M Hirayama
  • Q Jiang
  • S Iwamoto
  • T Kumamoto
  • H Yamamoto
  • M Sakurai
  • Y Komada
چکیده

Dendritic cell (DC) is the most potent activator of CD4+ T cells and has unique dendrites and veils. To explore the function of Rho in DC, exoenzyme C3 from Clostridium botulinum was used as a specific inhibitor of Rho. Treatment of DC with C3 (DC/C3) resulted in profound morphological changes by losing dendrites and emerging of shrunk membrane processes that were in parallel with marked reduction of polymerized actin in the marginal area. Inactivation of Rho-associated coiled coil-containing kinase (p160ROCK) by a specific ROCK inhibitor Y-27632 also led to disappearance of dendrites of DC with retaining large membrane expansions. In scanning electron microscopy, untreated DCs interacted with CD4+ T cells more efficiently than DC/C3. Conjugate formation assay showed that the number of DCs associated with CD4+ T cells was 2-fold higher in untreated DCs than that of DC/C3. Alloantigen-presenting capacity of DC/C3 was significantly suppressed in a dose-dependent manner. Because C3 treatment did not affect the surface expression of HLA, costimulatory, and adhesion molecules of DC, we examined cytokine production of DC and naive CD4+ T cells to further elucidate the inhibitory mechanism of MLR. Unexpectedly, DC/C3 increased IL-12 production after LPS stimulation. Naive CD4+ T cells cocultured with DC/C3 produced the increased percentage of IFN-gamma-producing cells, whereas the percentage of IL-2-producing T cells was decreased. These results demonstrate that Rho GTPase in DC controls both characteristic shape and immunogenic capacity.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

تولید سلول های دندریتیک مهاری و سلول های شبه ماکروفاژی با استفاده ترکیبی از فاکتورهای بلوغ

Background and purpose: As professional antigen- presenting cells, dendritic cells are a bridge between innate and adaptive immunity by stimulating T lymphocytes. Recent research has demonstrated the extra ability of the myeloid cells plasticity into different cells in response to environmental stimuli. In the present study, the effect of using combination maturation factors (MCM, TNF-α, poly (...

متن کامل

Isolation and Phenotyping of Normal Mouse Liver Dendritic Cells by an Improved Method

Introduction Dendritic cells (DCs) are bone marrow-derived cells, which migrate to lymphoid and non-lymphoid organs via blood. Liver DCs are believed to play an important role in the regulation of hepatic allograft acceptance. However, because of inherent difficulties in isolating adequate numbers of DCs from liver, limited information is available on the phenotype and functions of liver DCs. ...

متن کامل

I-28: Role of Mevalonate-Ras Homology (Rho)/Rho-Associated Coiled-Coil-Forming Protein Ki nase-Mediated Signaling Pathway in The Pathogenesis of Endometriosis-Associated Fibrosis

Background: Endometriosis, a disease affecting 3-10% of women of reproductive age, is characterized by the ectopic growth of endometrial glands and stroma surrounded by dense fibrous tissue. Whereas, normal eutopic endometrium shows scarless tissue repair during menstrual cycles, which suggests that the endometriotic tissues have distinct mechanisms of fibrogenesis. During the development of en...

متن کامل

PICK1 links AMPA receptor stimulation to Cdc42

Rho-family GTPases control numerous cell biological processes via effects on actin dynamics, such as cell migration, cell adhesion, morphogenesis and vesicle traffic. In neurons, they are involved in dendritic spine morphogenesis and other aspects of neuronal morphology via regulation of the actin cytoskeleton. The Rho-family member Cdc42 regulates dendritic spine morphology via its effector N-...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of immunology

دوره 167 7  شماره 

صفحات  -

تاریخ انتشار 2001