TITLE:
Fyn Expression Predicates Both Protective Immunity and Onset of Autoimmunity
AUTHORS:
Behrouz Moemeni, Nathalie Vacaresse, Marina Vainder, Michael E. Wortzman, Tania H. Watts, André Veillette, Thomas F. Gajewski, Michael Julius
KEYWORDS:
Fyn, Lck, TcR Signaling, Immunity, Autoimmunity
JOURNAL NAME:
Open Journal of Immunology,
Vol.5 No.5,
December
3,
2015
ABSTRACT: Genomic disruption of Fyn has not been associated with an immune-deficient phenotype, notwithstanding the profound impairment in IL-2 production by T cells derived from Fyn-deficient animals observed in vitro. The results presented demonstrate that Fyn deficient animals succumb to influenza infection ahead of the protective expansion of lung infiltrating T cells and viral clearance observed in wild-type hosts. Formal proof that Fyn-dependent IL-2 production mediates T cell expansion in vivo is provided using a model of T cell induced enteropathy. Specifically, Fyn deficient naive T cells do not induce colitis in SCID animals due to their lack of expansion, and Fyn re-expression rescues both IL-2 production and its capacity to support in vivo expansion leading to colitis. These results reconcile the obligatory role of Fyn in T cell activation and autocrine IL-2 supported growth; and underscore the mechanism through which its function is integrated with and regulated by Lck.