IL-21 Receptor Signaling Is Essential for Optimal CD4 + T Cell Function and Control of Mycobacterium tuberculosis Infection in Mice

• Published in: The Journal of immunology (1950) Vol. 199; no. 8; pp. 2815 - 2822
• Main Authors: Cheekatla, Satyanarayana Swamy, Tripathi, Deepak, Venkatasubramanian, Sambasivan, Paidipally, Padmaja, Welch, Elwyn, Tvinnereim, Amy R, Nurieva, Roza, Vankayalapati, Ramakrishna
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 15.10.2017
• Subjects: Animals; Bacteria; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell Proliferation; Cells, Cultured; Chemokine receptors; Female; Humans; Infections; Interferon; Interferon-gamma - metabolism; Interleukin 21; Lung - immunology; Lung - microbiology; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Macrophages; Macrophages - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Optimal control; Receptors, Interleukin-21 - genetics; Receptors, Interleukin-21 - metabolism; Rodents; Signal Transduction; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; Tuberculosis; Tuberculosis - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1601231

In this study, we determined the role of IL-21R signaling in infection, using IL-21R knockout (KO) mice. A total of 50% of H37Rv infected IL-21R KO mice died in 6 mo compared with no deaths in infected wild type (WT) mice. infected IL-21R KO mice had enhanced bacterial burden and reduced infiltration of Ag-specific T cells in lungs compared with infected WT mice. Ag-specific T cells from the lungs of infected IL-21R KO mice had increased expression of T cell inhibitory receptors, reduced expression of chemokine receptors, proliferated less, and produced less IFN- γ, compared with Ag-specific T cells from the lungs of infected WT mice. T cells from infected IL-21R KO mice were unable to induce optimal macrophage responses to This may be due to a decrease in the Ag-specific T cell population. We also found that IL-21R signaling is associated with reduced expression of a transcriptional factor Eomesodermin and enhanced functional capacity of Ag-specific T cells of infected mice. The sum of our findings suggests that IL-21R signaling is essential for the optimal control of infection.