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Published on: March 2, 2014
Mice lacking protein tyrosine kinase fyn develop a T helper-type 1 response and resistLeishmania major infection
K Yamakami1, S Akao, K Wakabayashi
1Department of Public Health, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa, Saitama, Japan, yamakami@cc.ndme.ac.jp.
Abstract:
Fyn is a Src family protein tyrosine kinase associated with TCR/CD3 complex. Fyn appears to play a role in the activation of T cells based on its enzymatic activation and tyrosine phosphorylation following the ligation of TCR/CD3, and it also plays a critical role in the calcium flux and interleukin-2 (IL-2) production. The protective response against murineLeishmania major infection is associated with the T helper-type 1 (Th1) responses and the ability to modulate Th1 cytokines such as IL-2 and interferon-γ, respectively. The role of Fyn tyrosine kinasein vivo was directly examined by the response to infection withL. major in C57BL/6fyn-deficient mice. Despite the absence of Fyn, the mice remained resistant to this infection with only mild lesion development, and, they demonstrated Th1 responses as assessed by the delayed-type hyper-sensitivity response and cytokine milieu. The findings in thefyn-deficient mice failed to support a relationship between the anticipated functions of Fynin vitro and the immune response toL. major infectionin vivo. As a result, in leishmanial disease, Fyn probably plays a minor role in the protective immune response and is, therefore, not a key factor in such a response.
Insights
Mice lacking Fyn tyrosine kinase remained resistant to Leishmania major infection, showing normal T helper-type 1 (Th1) responses. This suggests Fyn plays a minor role in the immune defense against leishmaniasis.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Fyn is a Src family protein tyrosine kinase crucial for T cell activation, calcium flux, and IL-2 production.
- The protective immune response against Leishmania major infection involves T helper-type 1 (Th1) responses and cytokines like IL-2 and interferon-gamma.
Purpose of the Study:
- To investigate the in vivo role of Fyn tyrosine kinase in the immune response to Leishmania major infection.
- To determine if Fyn deficiency impacts resistance and Th1 responses in mice infected with Leishmania major.
Main Methods:
- Utilized C57BL/6fyn-deficient mice to examine the in vivo role of Fyn.
- Assessed resistance to Leishmania major infection by monitoring lesion development.
- Evaluated Th1 responses through delayed-type hypersensitivity and cytokine analysis.
Main Results:
- Fyn-deficient mice exhibited resistance to Leishmania major infection with only mild lesion development.
- These mice maintained robust Th1 responses, including delayed-type hypersensitivity and appropriate cytokine production.
- The in vivo findings did not correlate with the anticipated in vitro functions of Fyn in T cell activation.
Conclusions:
- Fyn tyrosine kinase appears to play a minor role in the protective immune response against Leishmania major infection.
- Fyn is not a key factor in the host's defense mechanisms against leishmaniasis.
- The in vitro functions of Fyn may not directly translate to its role in vivo during leishmanial disease.
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