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Abstract

Interleukin-7 (IL-7) is a cytokine with well-established roles in lymphocyte development in the bone marrow and thymus. Recent discoveries have expanded IL-7’s contribution to enhancing the effector responses of CD8 T cells in chronic LCMV infection and tumor clearance. IL-7Rα is highly expressed by mature lymphocytes in the lungs, but how IL-7 directs their function in acute airway viral infections is unclear. Using multiple mouse models, I show in chapter 3 that loss of IL-7 signaling results in impaired production of IL-5 and IL-13 in lung group two innate lymphoid cells (ILC2s) following influenza infection. Conversely, mice treated with IL-7 have increased production of IL-5 and IL-13 by lung ILC2s. Moreover, I show that IL-7 regulates GATA3 and CD25 expression in lung and bone marrow ILC2s. However, IL-7 is non-essential for the expression of the anti-apoptotic protein Bcl-2 and survival of ILC2s. In chapter 4, I show that IL-7 signaling plays an important role in CD8 T cell responses to acute influenza infection. Specifically, IL-7Rα is required for a normal sized mediastinal lymph node and the expansion of influenza-specific CD8 T cells therein. Terminal differentiation of influenza-specific CD8 T cells requires normal IL-7 signaling as well. Interestingly, IL-7 also plays a selective role in enhancing the effector function of influenza-specific CD8 T cells depending on their antigen specificity. Finally, IL-7 is inducible in the lungs by multiple cellular sources following viral infection. These findings on IL-7 and its effects on lower respiratory diseases will be important for expanding the utility of therapeutics that are currently available.