Interleukin-7 is required for CD4+ T cell activation and autoimmune neuroinflammation

Brian R. Lawson; Rosana Gonzalez-Quintial; Theodoros Eleftheriadis; Michael A. Farrar; Stephen D. Miller; Karsten Sauer; Dorian B. McGavern; Dwight H. Kono; Roberto Baccala; Argyrios N. Theofilopoulos

doi:10.1016/j.clim.2015.08.007

Interleukin-7 is required for CD4⁺ T cell activation and autoimmune neuroinflammation

Brian R. Lawson, Rosana Gonzalez-Quintial, Theodoros Eleftheriadis, Michael A. Farrar, Stephen D. Miller, Karsten Sauer, Dorian B. McGavern, Dwight H. Kono, Roberto Baccala, Argyrios N. Theofilopoulos^*

^*Corresponding author for this work

Microbiology-Immunology

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

IL-7 is known to be vital for T cell homeostasis but has previously been presumed to be dispensable for TCR-induced activation. Here, we show that IL-7 is critical for the initial activation of CD4⁺ T cells in that it provides some of the necessary early signaling components, such as activated STAT5 and Akt. Accordingly, short-term in vivo IL-7Rα blockade inhibited the activation and expansion of autoantigen-specific CD4⁺ T cells and, when used to treat experimental autoimmune encephalomyelitis (EAE), prevented and ameliorated disease. Our studies demonstrate that IL-7 signaling is a prerequisite for optimal CD4⁺ T cell activation and that IL-7R antagonism may be effective in treating CD4⁺ T cell-mediated neuroinflammation and other autoimmune inflammatory conditions.

Original language	English (US)
Pages (from-to)	260-269
Number of pages	10
Journal	Clinical Immunology
Volume	161
Issue number	2
DOIs	https://doi.org/10.1016/j.clim.2015.08.007
State	Published - Dec 1 2015

Funding

This is manuscript number 29180 from the Department of Immunology and Microbial Science of The Scripps Research Institute. We would like to thank M. Kat Occhipinti for editorial assistance, and John Scatizzi, Dilki Wichramarachchi, and Tannaz Hasnat for excellent technical assistance. This work was supported by grant AR065919 from the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases .

Keywords

EAE
IL-7
Signaling pathways
T cells

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.1016/j.clim.2015.08.007

Cite this

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title = "Interleukin-7 is required for CD4+ T cell activation and autoimmune neuroinflammation",

abstract = "IL-7 is known to be vital for T cell homeostasis but has previously been presumed to be dispensable for TCR-induced activation. Here, we show that IL-7 is critical for the initial activation of CD4+ T cells in that it provides some of the necessary early signaling components, such as activated STAT5 and Akt. Accordingly, short-term in vivo IL-7Rα blockade inhibited the activation and expansion of autoantigen-specific CD4+ T cells and, when used to treat experimental autoimmune encephalomyelitis (EAE), prevented and ameliorated disease. Our studies demonstrate that IL-7 signaling is a prerequisite for optimal CD4+ T cell activation and that IL-7R antagonism may be effective in treating CD4+ T cell-mediated neuroinflammation and other autoimmune inflammatory conditions.",

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AU - Lawson, Brian R.

AU - Gonzalez-Quintial, Rosana

AU - Eleftheriadis, Theodoros

AU - Farrar, Michael A.

AU - Miller, Stephen D.

AU - Sauer, Karsten

AU - McGavern, Dorian B.

AU - Kono, Dwight H.

AU - Baccala, Roberto

AU - Theofilopoulos, Argyrios N.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - IL-7 is known to be vital for T cell homeostasis but has previously been presumed to be dispensable for TCR-induced activation. Here, we show that IL-7 is critical for the initial activation of CD4+ T cells in that it provides some of the necessary early signaling components, such as activated STAT5 and Akt. Accordingly, short-term in vivo IL-7Rα blockade inhibited the activation and expansion of autoantigen-specific CD4+ T cells and, when used to treat experimental autoimmune encephalomyelitis (EAE), prevented and ameliorated disease. Our studies demonstrate that IL-7 signaling is a prerequisite for optimal CD4+ T cell activation and that IL-7R antagonism may be effective in treating CD4+ T cell-mediated neuroinflammation and other autoimmune inflammatory conditions.

AB - IL-7 is known to be vital for T cell homeostasis but has previously been presumed to be dispensable for TCR-induced activation. Here, we show that IL-7 is critical for the initial activation of CD4+ T cells in that it provides some of the necessary early signaling components, such as activated STAT5 and Akt. Accordingly, short-term in vivo IL-7Rα blockade inhibited the activation and expansion of autoantigen-specific CD4+ T cells and, when used to treat experimental autoimmune encephalomyelitis (EAE), prevented and ameliorated disease. Our studies demonstrate that IL-7 signaling is a prerequisite for optimal CD4+ T cell activation and that IL-7R antagonism may be effective in treating CD4+ T cell-mediated neuroinflammation and other autoimmune inflammatory conditions.

KW - EAE

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KW - Signaling pathways

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