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 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 neighbors 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.

      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.

Research Projects:

      1. Elucidating the roles of interferon signaling in the adult mammalian central nervous system (CNS) under homeostasis and after injury.
2. Studying the roles of lipid-associated macrophages in CNS injury and repair.
3. Uncovering tissue communication circuits underlying selective neuronal resilience.
4. Exploring neuroimmune circuits that underlie peripheral tissue regeneration.

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).