Felipe A Pinho-Ribeiro and Isaac M Chiu. 11/2019. “
Nociceptor nerves set the stage for skin immunity.” Cell Res, 29, 11, Pp. 877-878.
PDF Antonia Wallrapp, Patrick R Burkett, Samantha J Riesenfeld, Se-Jin Kim, Elena Christian, Raja-Elie E Abdulnour, Pratiksha I Thakore, Alexandra Schnell, Conner Lambden, Rebecca H Herbst, Pavana Khan, Kazutake Tsujikawa, Ramnik J Xavier, Isaac M Chiu, Bruce D Levy, Aviv Regev, and Vijay K Kuchroo. 10/15/2019. “
Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses.” Immunity, 51, 4, Pp. 709-723.e6.
AbstractNeuroimmune interactions have emerged as critical modulators of allergic inflammation, and type 2 innate lymphoid cells (ILC2s) are an important cell type for mediating these interactions. Here, we show that ILC2s expressed both the neuropeptide calcitonin gene-related peptide (CGRP) and its receptor. CGRP potently inhibited alarmin-driven type 2 cytokine production and proliferation by lung ILC2s both in vitro and in vivo. CGRP induced marked changes in ILC2 expression programs in vivo and in vitro, attenuating alarmin-driven proliferative and effector responses. A distinct subset of ILCs scored highly for a CGRP-specific gene signature after in vivo alarmin stimulation, suggesting CGRP regulated this response. Finally, we observed increased ILC2 proliferation and type 2 cytokine production as well as exaggerated responses to alarmins in mice lacking the CGRP receptor. Together, these data indicate that endogenous CGRP is a critical negative regulator of ILC2 responses in vivo.
PDF Kimbria J Blake, Xin Ru Jiang, and Isaac M Chiu. 8/2019. “
Neuronal Regulation of Immunity in the Skin and Lungs.” Trends Neurosci, 42, 8, Pp. 537-551.
AbstractThe nervous and immune systems are classically studied as two separate entities. However, their interactions are crucial for maintaining barrier functions at tissues constantly exposed to the external environment. We focus here on the role of neuronal signaling in regulating the immune system at two major barriers: the skin and respiratory tract. Barrier tissues are heavily innervated by sensory and autonomic nerves, and are densely populated by resident immune cells, allowing rapid, coordinated responses to noxious stimuli, as well as to bacterial and fungal pathogens. Neural release of neurotransmitters and neuropeptides allows fast communication with immune cells and their recruitment. In addition to maintaining homeostasis and fighting infections, neuroimmune interactions are also implicated in several chronic inflammatory conditions such as atopic dermatitis (AD), chronic obstructive pulmonary disease (COPD), and asthma.
PDF Pankaj Baral, Swalpa Udit, and Isaac M Chiu. 7/2019. “
Pain and immunity: implications for host defence.” Nat Rev Immunol, 19, 7, Pp. 433-447.
AbstractPain is a hallmark of tissue injury, inflammatory diseases, pathogen invasion and neuropathy. It is mediated by nociceptor sensory neurons that innervate the skin, joints, bones, muscles and mucosal tissues and protects organisms from noxious stimuli. Nociceptors are sensitized by inflammatory mediators produced by the immune system, including cytokines, lipid mediators and growth factors, and can also directly detect pathogens and their secreted products to produce pain during infection. Upon activation, nociceptors release neuropeptides from their terminals that potently shape the function of innate and adaptive immune cells. For some pathogens, neuron-immune interactions enhance host protection from infection, but for other pathogens, neuron-immune signalling pathways can be exploited to facilitate pathogen survival. Here, we discuss the role of nociceptor interactions with the immune system in pain and infection and how understanding these pathways could produce new approaches to treat infectious diseases and chronic pain.
PDF Tiphaine Voisin and Isaac M Chiu. 5/21/2019. “
Mast Cells Get on Your Nerves in Itch.” Immunity, 50, 5, Pp. 1117-1119.
AbstractMast-cell-nerve interactions play an integral role in itch and inflammation. Meixiong et al. (2019) show that the receptors MRGPRB2 and FcεRI mediate distinct types of mast cell activation and nerve interactions and that mast cell activation through MRGPRB2 drives itch in allergic contact dermatitis.
PDF Juan-Manuel Leyva-Castillo, Claire Galand, Christy Kam, Oliver Burton, Michael Gurish, Melissa A Musser, Jeffrey D Goldsmith, Elizabeth Hait, Samuel Nurko, Frank Brombacher, Chen Dong, Fred D Finkelman, Richard T Lee, Steven Ziegler, Isaac Chiu, Frank K Austen, and Raif S Geha. 5/21/2019. “
Mechanical Skin Injury Promotes Food Anaphylaxis by Driving Intestinal Mast Cell Expansion.” Immunity, 50, 5, Pp. 1262-1275.e4.
AbstractMast cell (MC) mediator release after crosslinking of surface-bound IgE antibody by ingested antigen underlies food allergy. However, IgE antibodies are not uniformly associated with food allergy, and intestinal MC load is an important determinant. Atopic dermatitis (AD), characterized by pruritis and cutaneous sensitization to allergens, including foods, is strongly associated with food allergy. Tape stripping mouse skin, a surrogate for scratching, caused expansion and activation of small intestinal MCs, increased intestinal permeability, and promoted food anaphylaxis in sensitized mice. Tape stripping caused keratinocytes to systemically release interleukin-33 (IL-33), which synergized with intestinal tuft-cell-derived IL-25 to drive the expansion and activation of intestinal type-2 innate lymphoid cells (ILC2s). These provided IL-4, which targeted MCs to expand in the intestine. Duodenal MCs were expanded in AD. In addition to promoting cutaneous sensitization to foods, scratching may promote food anaphylaxis in AD by expanding and activating intestinal MCs.
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