Inter-organ Communication in Wound Healing
(Top) Injury activates JAK/STAT in both visceral muscles and intestinal progenitor cells. Immunostaining revealed an expansion of the GFP signal in the guts upon clean or septic injury in wild-type flies.
(Middle Left and Right) Knockdown of either upd2 or upd3 in haemocytes increased the susceptibility of flies to wounding, while only the knockdown of upd3 resulted in higher susceptibility to septic injury with Ecc15.
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(Bottom) STAT activation 2 days post clean injury in the muscle, Intestinal stem cells, and enterocytes.
An Organism throughout its lifetime will encounter several events that will cause damage to its organs and tissues. Tissue damage can activate both local tissues and organs at the far via local responses and systemic wound responses within the host for which interorgan communication becomes crucial to mediate homeostasis and survival. Cells have evolved to mount both local communication and distant communication through mechanisms that ultimately help the organism to heal the wound at the wound site and also communicate the wound to distant organs to bring about necessary modulations that benefit the organism’s overall survival.
In Drosophila and mammals, the intestine is an organ that is proven to show dynamic plasticity at the onset of events like injury, infection, and damage to the host. The Intestine mediates nutrient absorption, immune response and is a vital organ that also responds to distant wounds.
Hemocytes, the blood cells in drosophila have vital functions such as mounting immune response, and tissue remodeling and are also a signaling hub that can mediate immune response to distant tissues. The JAK/STAT pathway is one of the key signaling pathways involved in the regulation of development and immunity in Drosophila and humans. There are multiple reports that have suggested previously that this pathway regulates proliferation and differentiation as it plays a pivotal role in intestinal stem cell (ISC) activity. Despite extensive studies, the crosstalk between hemocytes and the JAK-STAT pathway in the gut remains elusive.
Our work previously has demonstrated that upon injury and septic injury, hemocytes produce upd3 the cytokine homolog of IL6, that activates the JAK/STAT pathway in the Drosophila gut to regulate intestinal stem cell proliferation. This upd3 production has proven to be critical to survival upon injury.
Using Drosophila as a model, we aim to uncover how hemocyte-derived factors influence ISC behavior during wound healing. We further seek to identify the role of STAT activation in the drosophila gut and its influence on the molecular players that regulate intestinal homeostasis. This research will provide valuable insights into the cellular and molecular mechanisms governing intestinal homeostasis upon wounding.
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1. Intramacrophage ROS Primes the Innate Immune System via JAK/STAT and Toll Activation.
S. Chakrabarti*, and S. S. Visweswariah.
Cell Reports 2020. https://doi.org/10.1016/j.celrep.2020.108368 PMID: 33176146
2. Remote control of intestinal stem cell activity by hemocytes in Drosophila.
S. Chakrabarti*, JP. Dudzic, X. Li, EJ. Collas, JP Boquete, M. Poidevin, and B. Lemaitre*.
PLoS Genetics 2016. https://doi.org/10.1371/journal.pgen.1006089 PMID: 27231872