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Lnk prevents inflammatory CD8⁺ T-cell proliferation and contributes to intestinal homeostasis.
- Source :
-
European journal of immunology [Eur J Immunol] 2014 Jun; Vol. 44 (6), pp. 1622-32. Date of Electronic Publication: 2014 May 02. - Publication Year :
- 2014
-
Abstract
- The intracellular adaptor Lnk (also known as SH2B3) regulates cytokine signals that control lymphohematopoiesis, and Lnk(-/-) mice have expanded B-cell, megakaryocyte, and hematopoietic stem-cell populations. Moreover, mutations in the LNK gene are found in patients with myeloproliferative disease, whereas LNK 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(+) T-cell proliferation and in intestinal homeostasis. Mature T cells from newly generated Lnk-Venus reporter mice had low but substantial expression of Lnk, whereas Lnk expression was downregulated during homeostatic T-cell proliferation under lymphopenic conditions. The numbers of CD44(hi) IFN-γ(+) CD8(+) effector or memory T cells were found to be increased in Lnk(-/-) mice, which also exhibited shortening of villi in the small intestine. Lnk(-/-) CD8(+) T cells survived longer in response to stimulation with IL-15 and proliferated even in nonlymphopenic hosts. Transfer of Lnk(-/-) CD8(+) T cells together with WT CD4(+) T cells into Rag2-deficient mice recapitulated a sign of villous abnormality. Our results reveal a link between Lnk and immune cell-mediated intestinal tissue destruction.<br /> (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Adaptor Proteins, Signal Transducing
Animals
CD8-Positive T-Lymphocytes pathology
DNA-Binding Proteins genetics
DNA-Binding Proteins immunology
Homeostasis genetics
Hyaluronan Receptors genetics
Hyaluronan Receptors immunology
Inflammation genetics
Inflammation immunology
Inflammation pathology
Intestines pathology
Intracellular Signaling Peptides and Proteins genetics
Membrane Proteins
Mice
Mice, Knockout
Polymorphism, Genetic immunology
CD8-Positive T-Lymphocytes immunology
Cell Proliferation
Homeostasis immunology
Intestines immunology
Intracellular Signaling Peptides and Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-4141
- Volume :
- 44
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 24536025
- Full Text :
- https://doi.org/10.1002/eji.201343883