Activating transcription factor 5 (ATF5) controls intestinal tuft and goblet cell expansion upon succinate-induced type 2 immune responses in mice.

Intestinal tuft cells, a chemosensory cell type in mucosal epithelia that secrete interleukin (IL)-25, play a pivotal role in type 2 immune responses triggered by parasitic infections. Tuft cell-derived IL-25 activates type 2 innate lymphoid cells (ILC2) to secrete IL-13, which, in turn, acts on intestinal stem or transient amplifying cells to expand tuft cells themselves and mucus-secreting goblet cells. However, the molecular mechanisms of tuft cell differentiation under type 2 immune responses remain unclear. The present study investigated the effects of the deletion of activating transcription factor 5 (ATF5) on the type 2 immune response triggered by succinate (a metabolite of parasites) in mice. ATF5 mRNAs were expressed in the small intestine, and the loss of the ATF5 gene did not affect the gross morphology of the tissue or the basal differentiation of epithelial cell subtypes. Succinate induced marked increases in tuft and goblet cell numbers in the ATF5-deficient ileum. Tuft cells in the ATF5-deficient ileum are assumed to be a subtype of intestinal tuft cells (Tuft-2 cells) marked by the transcription factor Spib. Exogenous IL-25 induced similar increases in tuft and goblet cell numbers in wild-type and ATF5-deficient ilea. IL-13 at a submaximal dose enhanced tuft cell differentiation more in ATF5-deficient than in wild-type intestinal organoids. These results indicate that the loss of ATF5 enhanced the tuft cell-ILC2 type 2 immune response circuit by promoting tuft cell differentiation in the small intestine, suggesting its novel regulatory role in immune responses against parasitic infections.

Hereditary Angioedema with Recurrent Abdominal Pain in a Patient with a Novel Mutation.

We describe a patient with hereditary angioedema type I. The patient had experienced recurrent abdominal pain around the time of her menstrual period for 13 years. A laboratory examination showed reduced functional and antigenic levels of C4 and C1 inhibitor (C1-INH). To establish a diagnosis, we carried out a DNA analysis of the patient's C1-INH gene. We determined that the patient was heterozygous for a single base pair transposition of T to C at nucleotide 4429 in exon 4, which had not been reported in the literature. As the patient had no family history of hereditary diseases, it was considered to be a de novo mutation.

A leiomyomatoid angiomatous neuroendocrine tumor of the myometrium: case study with ultrastructural analysis.

Leiomyomatoid angiomatous neuroendocrine tumor (LANT) is a possible new disease entity that was described as a dimorphic neurosecretory tumor with a leiomyomatous vascular component; it was found in the pituitary. We describe here a second case of LANT in a 45-year-old woman with a myometrial tumor, diagnosed clinically as uterine leiomyoma. She underwent laparoscopic myomectomy. The tumor consisted of hyalinized vasculature, containing factor VIII-positive endothelium and smooth muscle actin-positive vascular smooth muscle cells, and stromal cells, expressing neuroadhesion molecules. Both vascular and stromal components diffusely expressed chromogranin A and, as evidenced by electron microscopy, possessed smooth muscle actin filaments and electron-dense neurosecretory granules, which contained the neurosecretory hormone somatostatin. Although no cytokeratin-positive cells were observed, some tumor cells had positive Grimelius staining for argyrophilic granules. These findings meet the definition of LANT, and the occurrence of our case suggests that LANT is a special type of neuroendocrine neoplasm and is not organ specific.