T cells in the brains of Toxoplasma-infected mice are shown to move by Lévy-like walks. T cells are an important first point of contact between the immune system and invading pathogens. The currently accepted model of the early stages of the immune reaction, in which the T cells encounter the invader, is that of a Brownian random walk. This paper reports the use of in vivo multiphoton microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the protozoon pathogen Toxoplasma gondii. Surprisingly, the in vivo imaging reveals that T cells in the brains of mice infected with T. gondii move not by Brownian-type motion but instead follow a Lévy walk pattern of runs punctuated by periodic pauses. Mathematical simulations suggest that this mode of movement increases the chances of finding targets at unknown locations. Chemokines have a central role in regulating processes essential to the immune function of T cells1,2,3, such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the pathogen Toxoplasma gondii in the brains of chronically infected mice. This chemokine boosts T-cell function in two different ways: it maintains the effector T-cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Notably, these statistics are not Brownian; rather, CD8+ T-cell motility in the brain is well described by a generalized Lévy walk. According to our model, this unexpected feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8+ T-cell behaviour is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys4,5,6,7,8,9,10, and CXCL10 aids T cells in shortening the average time taken to find rare targets.

The cell-intrinsic pathways controlling the function of innate lymphoid cells are poorly defined. Artis and colleagues demonstrate that ILC2s selectively express arginase 1 and that this is critical for their bioenergetics, proliferation and function. Group 2 innate lymphoid cells (ILC2s) regulate tissue inflammation and repair after activation by cell-extrinsic factors such as host-derived cytokines. However, the cell-intrinsic metabolic pathways that control ILC2 function are undefined. Here we demonstrate that expression of the enzyme arginase-1 (Arg1) during acute or chronic lung inflammation is a conserved trait of mouse and human ILC2s. Deletion of mouse ILC-intrinsic Arg1 abrogated type 2 lung inflammation by restraining ILC2 proliferation and dampening cytokine production. Mechanistically, inhibition of Arg1 enzymatic activity disrupted multiple components of ILC2 metabolic programming by altering arginine catabolism, impairing polyamine biosynthesis and reducing aerobic glycolysis. These data identify Arg1 as a key regulator of ILC2 bioenergetics that controls proliferative capacity and proinflammatory functions promoting type 2 inflammation.

Type 2 inflammation underlies allergic diseases such as atopic dermatitis, which is characterized by the accumulation of basophils and group 2 innate lymphoid cells (ILC2s) in inflamed skin lesions. Although murine studies have demonstrated that cutaneous basophil and ILC2 responses are dependent on thymic stromal lymphopoietin, whether these cell populations interact to regulate the development of cutaneous type 2 inflammation is poorly defined. In this study, we identify that basophils and ILC2s significantly accumulate in inflamed human and murine skin and form clusters not observed in control skin. We demonstrate that murine basophil responses precede ILC2 responses and that basophils are the dominant IL-4–enhanced GFP-expressing cell type in inflamed skin. Furthermore, basophils and IL-4 were necessary for the optimal accumulation of ILC2s and induction of atopic dermatitis–like disease. We show that ILC2s express IL-4Rα and proliferate in an IL-4–dependent manner. Additionally, basophil-derived IL-4 was required for cutaneous ILC2 responses in vivo and directly regulated ILC2 proliferation ex vivo. Collectively, these data reveal a previously unrecognized role for basophil-derived IL-4 in promoting ILC2 responses during cutaneous inflammation.