Loss of Function of the Mouse Sharpin Gene Results in Peyer’s Patch Regression

Rosemarie Seymour,John P. Sundberg,Leonard D. Shultz,Bobbi-Jo Shirley,Harm HogenEsch,Mehrdad Matloubian

doi:10.1371/journal.pone.0055224

Rosemarie Seymour, John P. Sundberg + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0055224

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Journal: PloS one	Publication Date: Feb 12, 2013
Citations: 52	License type: CC BY 4.0

Affiliation: Jackson Laboratory, Purdue University West Lafayette

Abstract

Peyer’s patches (PP) are an important component in the immune response against intestinal pathogens. Two independent, spontaneous mutations in the mouse Sharpin gene (Sharpincpdm and Sharpincpdm-Dem) result in the absence of PP and disrupted splenic white pulp in adult mice, although a full complement of lymph nodes is present. Here we report that rudimentary PP begin to develop in Sharpincpdm mice during embryogenesis, but lack the organizational patterns that are typical of this tissue. In the present study, small intestines examined at weekly intervals from birth to maturity showed spontaneous regression of PP in mutant mice with concurrent infiltration of granulocytes. At 5 to 6 weeks of age, only indistinct remnants of granulocytic accumulations remain. Transplantation of normal bone marrow into Sharpincpdm mice at 7 days of age did not prevent regression of PP in bone marrow chimeras examined at 7 to 8 weeks of age. These findings indicate that SHARPIN expression is required for the normal development and maintenance, but not initiation, of PP.

Highlights

Peyer’s patches (PP) are organized secondary lymphoid tissues located in the anti-mesenteric wall of the small intestine of mammals
Early lymph sacs bud from vascular endothelium in a prospero-related homeobox 1 (PROX1)-dependent manner to accumulate lymphoid tissue inducer (LTi) cells, while PP are initiated by the Ret proto-oncogene-dependent clustering of previously scattered LTi cells with KIT+, ITGAX (CD11C)+ initiator cells in the small intestine [8,9]
Development of splenic white pulp is not dependent on LTi cells, but its organization and maturation requires activation of nuclear factor kappa B (NFKB) through LTA1B2 signaling in lymphocytes [14]

Summary

Introduction

Peyer’s patches (PP) are organized secondary lymphoid tissues located in the anti-mesenteric wall of the small intestine of mammals. They comprise the major inductive sites for adaptive immune responses to intestinal antigens. PP development (reviewed in [2]) is a nuclear factor kappa B (NFKB)-dependent process initiated in the intestinal stroma of embryonic mice by vascular cell adhesion molecule 1 (VCAM1)+, intracellular adhesion molecule 1 (ICAM1)+ stromal organizer cells on the antimesenteric surface of the small intestine at 15.5 days post conception (dpc), followed by recruitment of lymphoid tissue inducer (LTi) cells. To begin to elucidate the mechanism underlying the absence of PP in adult Sharpincpdm mutant mice, the small intestines of neonatal and young mice homozygous for the recessive Sharpincpdm mutation were examined for evidence of PP anlagen. Spontaneous regression of PP in maturing Sharpincpdm mice was typically associated with infiltration by granulocytes

Results

Discussion

Methods