Neuroimmune circuits of tissue repair

Tissues are complex multicellular units in which different cell types work together to maintain function. In response to insult, wound healing and tissue regeneration mechanisms are activated, requiring delicate coordination between these cell types. Specifically, bidirectional interactions between the nervous and immune systems are emerging as central coordinators of tissue homeostasis and repair.

We study the dynamics of tissue injury and repair through a neuroimmune lens. We combine in vivo experimental models with leading-edge analysis approaches, including immunological assays, neuronal modulation, single-cell genomics and imaging techniques to analyze injury responses in the context of the entire tissue ecosystem. We reason that better understanding of the intricate multicellular circuits activated in response to insult can shed light on instances where repair is lacking. We hope to leverage our discoveries to help guide treatment of traumatic injuries and degenerative diseases.

Our studies revolve around two main themes:

1. What are the tissue determinants that dictate survival and regeneration of neurons?

              The adult mammalian central nervous system (CNS) has very limited capacity to regenerate, such that injury or disease may lead to irreversible loss of function. Some neurons                            survive better than their neighbours in response to a shared insult, providing an opportunity to explore mechanisms of resilience. Defining the multicellular pathways that are                            beneficial or detrimental to neuronal survival can potentially inform the design of neuroprotective interventions.

             As the gateway of visual information to the brain, the retina is the source and the target of many blinding conditions. We use models of retinal injury to find ways to rescue retinal                      neurons and preserve vision. Furthermore, the retina is a window to the brain, allowing us to study mechanisms of degeneration and repair that are relevant to the CNS at large.     

          2. How do neuroimmune interactions orchestrate regeneration in peripheral tissues?
               The role of the immune response in wound healing and regeneration of peripheral organs such as the liver or skin is well established. Less described, yet increasingly appreciated,                   is  the involvement of neuronal circuits within those organs in guiding tissue repair. Studies on sensory perception of tissue damage and subsequent communication with resident                   and immune cells may uncover ways to overcome barriers to repair.  

Publications:

1. Benhar I*, Ding J*, Yan W, Whitney IE, Jacobi A, Sud M, Burgin G, Shekhar K, Tran NM, Wang C, He Z, Sanes JR, Regev A. Temporal single cell atlas of non-neuronal retinal cells reveals dynamic, coordinated multicellular responses to central nervous system injury. Nature Immunology 24, 700-713 (2023). doi: https://doi.org/10.1038/s41590-023-01437-w.
2. Jacobi A*, Tran NM*, Yan W*, Benhar I, Tian F, Schaffer R, He Z, Sanes JR. Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells. Neuron 110(16): 2625-2645 (2022).
3. Yan W*, Laboulaye MA*, Tran NM, Whitney IE, Benhar I, Sanes JR. Mouse Retinal Cell Atlas: Molecular Identification of over Sixty Amacrine Cell Types. J Neurosci 40(27):5177-5195 (2020).
4. Tran NM*, Shekhar K*, Whitney IE*, Jacobi A*, Benhar I, Hong G, Yan W, Adiconis X, Arnold ME, Lee JM, Levin JZ, Lin D, Wang C, Lieber CM, Regev A, He Z, Sanes JR. Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes. Neuron 104:1-17 (2019).
5. Benhar I, Abramson J. (2018) AIRE. In: Choi S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham, pg:255 -261
6. Benhar I, Reemst K, Kalchenko V, Schwartz M. The retinal pigment epithelium as a gateway for monocyte trafficking into the eye. EMBO J 35(11):1219-35 (2016). See video synopsis.
7. London A*, Benhar I*, Mattapallil MJ, Mack M, Caspi RR, Schwartz M. Functional macrophage heterogeneity in a mouse model of autoimmune central nervous system pathology. J Immunol 190(7):3570-8 (2013).
8. London A*, Benhar I*, Schwartz M. The retina as a window to the brain-from eye research to CNS disorders. Nat Rev Neurol 9(1):44-53 (2013).
9. Benhar I, London A, Schwartz M. The privileged immunity of immune privileged organs: The case of the eye. Frontiers in Immunology 3:296 (2012).
10. London A*, Itskovich E*, Benhar I*, Kalchenko V, Mack M, Jung S, Schwartz M. Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages. J Exp Med 208(1):23-39 (2011).

We are open to applications from enthusiastic scientists interested in joining our team!

Positions are available at all stages, including MSc, PhD and postdoc, as well as undergraduate students for part time projects.

To apply, please send your CV to inbal.benhar@mail.huji.ac.il.