Metabolic coordination between skin epithelium and type 17 immunity sustains chronic skin inflammation

Ipsita Subudhi, Piotr Konieczny, Aleksandr Prystupa, Rochelle L. Castillo, Erica Sze-Tu, Yue Xing, Daniel Rosenblum, Ilana Reznikov, Ikjot Sidhu, Cynthia Loomis, Catherine P. Lu, Niroshana Anandasabapathy, Mayte Suárez-Fariñas, Johann E. Gudjonsson, Aristotelis Tsirigos, Jose U. Scher, Shruti Naik

Inflammatory epithelial diseases are spurred by the concomitant dysregulation of immune and epithelial cells. How these two dysregulated cellular compartments simultaneously sustain their heightened metabolic demands is unclear. Single-cell and spatial transcriptomics (ST), along with immunofluorescence, revealed that hypoxia-inducible factor 1α (HIF1α), downstream of IL-17 signaling, drove psoriatic epithelial remodeling. Blocking HIF1α in human psoriatic […]


May 20, 2024

Inflammatory Memory in Chronic Skin Disease

Joseph A. Daccache, Shruti Naik

Inflammation is a hallmark of remitting-relapsing dermatological diseases. While a large emphasis has been placed on adaptive immune cells as mediators of relapse, evidence in epithelial and innate immune biology suggests that disease memory is widespread. Here we bring to fore the concept of inflammatory memory or non-specific training of long-lived cells in the skin, […]

JID Innovations

May 02, 2024

Staph aureus itch

Staphylococcus scratches its itch

Jack Major, Shruti Naik

Itch exacerbates infection and inflammation-associated skin pathology. In this issue of Cell, Deng et al. identify a V8 protease released by Staphylococcus aureus triggering itch via neuronal protease-activated receptor 1. In so doing, they uncover profound consequences of microbial neurosensory modulation and the ensuing scratch-induced tissue damage that potentiates infection.


April 10, 2024

Cis-regulatory arbitrators of regeneration

Piotr Konieczny, Shruti Naik

Mammals favor healing with scaring over functional tissue regeneration.1 In this issue of Cell Stem Cell, Mack et al. use “super-healer” mice to identify cis-regulatory variations that direct regenerative versus fibrotic gene expression in wound fibroblasts and they uncover complement factor H as a molecular driver of skin regeneration.

Cell Stem Cell

September 06, 2023

Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems

Rochelle L Castillo, Ikjot Sidhu, Igor Dolgalev, Tinyi Chu, Aleksandr Prystupa, Ipsita Subudhi, Di Yan, Piotr Konieczny, Brandon Hsieh, Rebecca H Haberman, Shanmugapriya Selvaraj, Tomoe Shiomi, Rhina Medina, Parvathy Vasudevanpillai Girija, Adriana Heguy, Cynthia A Loomis, Luis Chiriboga, Christopher Ritchlin, Maria De La Luz Garcia-Hernandez, John Carucci, Shane A Meehan, Andrea L Neimann, Johann E Gudjonsson, Jose U Scher, Shruti Naik

Whereas the cellular and molecular features of human inflammatory skin diseases are well characterized, their tissue context and systemic impact remain poorly understood. We thus profiled human psoriasis (PsO) as a prototypic immune-mediated condition with a high predilection for extracutaneous involvement. Spatial transcriptomics (ST) analyses of 25 healthy, active lesion, and clinically uninvolved skin biopsies […]

Science Immunology

June 02, 2023

Fast and scarless: Prx1+ fibroblasts turbocharge healing

Rachel M Kratofil, Shruti Naik

Our oral cavity has evolved a capacity for rapid healing without scarring. In this issue of JEM, Ko et al. (2022. J. Exp. Med. identify a Prx1+ fibroblast progenitor that drives oral regeneration by summoning pro-healing TGFβ1+ macrophages.

Journal of Experimental Medicine

March 06, 2023

Immune-Epithelial Cross Talk in Regeneration and Repair

Laure Guenin-Mace, Piotr Konieczny, Shruti Naik

The epithelial tissues that line our body, such as the skin and gut, have remarkable regenerative prowess and continually renew throughout our lifetimes. Owing to their barrier function, these tissues have also evolved sophisticated repair mechanisms to swiftly heal and limit the penetration of harmful agents following injury. Researchers now appreciate that epithelial regeneration and […]

Annual Review of Immunology

January 25, 2023

Langerhans cells are essential components of the angiogenic niche during murine skin repair

Renee Wasko, Kate Bridges, Rebecca Pannone, Ikjot Sidhu, Yue Xing, Shruti Naik, Kathryn Miller-Jensen, Valerie Horsley

Angiogenesis, the growth of new blood vessels from pre-existing vessels, occurs during development, injury repair, and tumorigenesis to deliver oxygen, immune cells, and nutrients to tissues. Defects in angiogenesis occur in cardiovascular and inflammatory diseases, and chronic, non-healing wounds, yet treatment options are limited. Here, we provide a map of the early angiogenic niche by […]

Developmental Cell

December 19, 2022

Inflammatory memory and tissue adaptation in sickness and in health

Shruti Naik, Elaine Fuchs

Our body has a remarkable ability to remember its past encounters with allergens, pathogens, wounds and irritants, and to react more quickly to the next experience. This accentuated sensitivity also helps us to cope with new threats. Despite maintaining a state of readiness and broadened resistance to subsequent pathogens, memories can also be maladaptive, leading […]


July 13, 2022

Interleukin-17 governs hypoxic adaptation of injured epithelium

Piotr Konieczny, Yue Xing, Ikjot Sidhu, Ipsita Subudhi, Kody P. Mansfield, Brandon Hsieh, Douglas E. Biancur, Samantha B. Larsen, Michael Cammer, Dongqing Li, Ning Xu Landén, Cynthia Loomis, Adriana Heguy, Anastasia N. Tikhonova, Aristotelis Tsirigos, and Shruti Naik

Mammalian cells autonomously activate hypoxia-inducible transcription factors (HIFs) to ensure survival in low-oxygen environments. We report here that injury-induced hypoxia is insufficient to trigger HIF1α in damaged epithelium. Instead, multimodal single-cell and spatial transcriptomics analyses and functional studies reveal that retinoic acid-related orphan receptor γt+ (RORγt+) γδ T cell-derived interleukin-17A (IL-17A) is necessary and sufficient to […]

Science Journal

July 08, 2022