Lnk prevents inflammatory CD8+ T‐cell proliferation and contributes to intestinal homeostasis. Issue 6 (2nd May 2014)

• Record Type: Journal Article
• Authors: Katayama, Hiroko; Mori, Taizo; Seki, Yoichi; Anraku, Masaki; Iseki, Masanori; Ikutani, Masashi; Iwasaki, Yukiko; Yoshida, Nobuaki; Takatsu, Kiyoshi; Takaki, Satoshi
• Is Part Of: European journal of immunology. Volume 44:Issue 6(2014:Jun.)
• Page Start: 1622
• Page End: 1632
• Publication Date: 2014-05-02
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201343883
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The intracellular adaptor Lnk (also known as SH2B3) regulates cytokine signals that control lymphohematopoiesis, and <italic>Lnk<sup>−/−</sup></italic> mice have expanded B‐cell, megakaryocyte, and hematopoietic stem‐cell populations. Moreover, mutations in the <italic>LNK</italic> gene are found in patients with myeloproliferative disease, whereas <italic>LNK</italic> polymorphisms have recently been associated with inflammatory and autoimmune diseases, including celiac disease. Here, we describe a previously unrecognized function of Lnk in the control of inflammatory CD8<sup>+</sup> T‐cell proliferation and in intestinal homeostasis. Mature T cells from newly generated <italic>Lnk</italic>–Venus reporter mice had low but substantial expression of <italic>Lnk</italic>, whereas <italic>Lnk</italic> expression was downregulated during homeostatic T‐cell proliferation under lymphopenic conditions. The numbers of CD44<sup>hi</sup>IFN‐γ<sup>+</sup>CD8<sup>+</sup> effector or memory T cells were found to be increased in <italic>Lnk<sup>−/−</sup></italic> mice, which also exhibited shortening of villi in the small intestine. <italic>Lnk<sup>−/−</sup></italic> CD8<sup>+</sup> T cells survived longer in response to stimulation with IL‐15 and proliferated even in nonlymphopenic hosts. Transfer of <italic>Lnk<sup>−/−</sup></italic> CD8<sup>+</sup> T cells together with WT CD4<sup>+</sup> T cells into <italic>Rag2</italic>‐deficient mice recapitulated a sign of villous abnormality. Our results reveal a link between Lnk and immune cell‐mediated intestinal tissue destruction.</p> </abstract>