Impaired Lymphocyte Trafficking in Mice Deficient in the Kinase Activity of PKN1

Overview

Journal Sci Rep

Specialty Science

Date 2017 Aug 11

PMID 28794483

Citations 8

Authors

Rana Mashud

Akira Nomachi

Akihide Hayakawa

Koji Kubouchi

Sally Danno

Takako Hirata

Kazuhiko Matsuo

Takashi Nakayama

Ryosuke Satoh

Reiko Sugiura

Manabu Abe

Kenji Sakimura

Shigeharu Wakana

Hiroyuki Ohsaki

Shingo Kamoshida

Hideyuki Mukai

Affiliations

Soon will be listed here.

Abstract

Knock-in mice lacking PKN1 kinase activity were generated by introducing a T778A point mutation in the catalytic domain. PKN1[T778A] mutant mice developed to adulthood without apparent external abnormalities, but exhibited lower T and B lymphocyte counts in the peripheral blood than those of wild-type (WT) mice. T and B cell development proceeded in an apparently normal fashion in bone marrow and thymus of PKN1[T778A] mice, however, the number of T and B cell counts were significantly higher in the lymph nodes and spleen of mutant mice in those of WT mice. After transfusion into WT recipients, EGFP-labelled PKN1[T778A] donor lymphocytes were significantly less abundant in the peripheral circulation and more abundant in the spleen and lymph nodes of recipient mice compared with EGFP-labelled WT donor lymphocytes, likely reflecting lymphocyte sequestration in the spleen and lymph nodes in a cell-autonomous fashion. PKN1[T778A] lymphocytes showed significantly lower chemotaxis towards chemokines and sphingosine 1-phosphate (S1P) than WT cells in vitro. The biggest migration defect was observed in response to S1P, which is essential for lymphocyte egress from secondary lymphoid organs. These results reveal a novel role of PKN1 in lymphocyte migration and localization.

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