Impaired mast cell maturation and degranulation and attenuated allergic responses in Ndrg1-deficient mice

Yoshitaka Taketormi, Kohei Sunaga, Satoshi Tanaka, Masanori Nakamura, Satoru Arata, Tomohiko Okuda, Tae Chul Moon, Hyeun Wook Chang, Yukihiko Sugimoto, Koichi Kokame, Toshiyuki Miyata, Makoto Murakami, Ichiro Kudo

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

We have previously reported that N-myc downstream regulated gene-1 (NDRG1) is an early inducible protein during the maturation of mouse bone marrow-derived mast cells (BMMCs) toward a connective tissue mast cell-like phenotype. To clarify the function of NDRG1 in mast cells and allergic responses, we herein analyzed mast cell-associated phenotypes of mice lacking the Ndrg1 gene. Allergic responses including IgE-mediated passive systemic and cutaneous anaphylactic reactions were markedly attenuated in Ndrg1-deficient mice as compared with those in wild-type mice. In Ndrg1-deficient mice, dermal and peritoneal mast cells were decreased in number and morphologically abnormal with impaired degranulating ability. Ex vivo, Ndrg1-deficient BMMCs cocultured with Swiss 3T3 fibroblasts in the presence of stem cell factor, a condition that facilitates the maturation of BMMCs toward a CTMC-like phenotype, displayed less exocytosis than replicate wild-type cells after the cross-linking of FcεRI or stimulation with compound 48/80, even though the exocytotic response of IL-3-maintained, immature BMMCs from both genotypes was comparable. Unlike degranulation, the production of leukotriene and cytokines by cocultured BMMCs was unaffected by NDRG1 deficiency. Taken together, the altered phenotypes of Ndrg1-deficient mast cells both in vivo and ex vivo suggest that NDRG1 has roles in the terminal maturation and elector function (degranulation) of mast cells.

Original languageEnglish
Pages (from-to)7042-7053
Number of pages12
JournalJournal of Immunology
Volume178
Issue number11
DOIs
Publication statusPublished - Jun 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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