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Choline acetyltransferase–expressing T cells are required to control chronic viral infection

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Science  08 Feb 2019:
Vol. 363, Issue 6427, pp. 639-644
DOI: 10.1126/science.aau9072

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ChAT-ty T cells fight viral infection

The neurotransmitter acetylcholine (ACh) is involved in processes such as muscle contraction, neuron communication, and vasodilation. Along with neurons, a population of immunological T cells and B cells express the enzyme choline acetyltransferase (ChAT), which catalyzes the rate-limiting step of ACh production. However, the role of immune cell–derived ACh is unclear. Cox et al. report that the cytokine interleukin-21 (IL-21) induces ChAT expression in CD4+ and CD8+ T cells during lymphocytic choriomeningitis virus infection (see the Perspective by Hickman). T cell–specific deletion of ChAT strongly impaired vasodilation and trafficking of antiviral T cells into infected tissues, which undermined the effective control of a chronic viral infection. Thus, IL-21 plays a critical role during chronic infection. Furthermore, the findings reveal a cholinergic mechanism that can regulate immune cell migration into tissues.

Science, this issue p. 639; see also p. 585

Abstract

Although widely studied as a neurotransmitter, T cell–derived acetylcholine (ACh) has recently been reported to play an important role in regulating immunity. However, the role of lymphocyte-derived ACh in viral infection is unknown. Here, we show that the enzyme choline acetyltransferase (ChAT), which catalyzes the rate-limiting step of ACh production, is robustly induced in both CD4+ and CD8+ T cells during lymphocytic choriomeningitis virus (LCMV) infection in an IL-21–dependent manner. Deletion of Chat within the T cell compartment in mice ablated vasodilation in response to infection, impaired the migration of antiviral T cells into infected tissues, and ultimately compromised the control of chronic LCMV clone 13 infection. Our results reveal a genetic proof of function for ChAT in T cells during viral infection and identify a pathway of T cell migration that sustains antiviral immunity.

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