Related Experiment Video
Updated: Mar 19, 2026
10:51
Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin
Published on: July 14, 2017
33.5K
RAC1 activation drives pathologic interactions between the epidermis and immune cells
The Journal of Clinical Investigation
|June 14, 2016
Summary
Ras-related C3 botulinum toxin substrate 1 (RAC1) is crucial for skin dysfunction in psoriasis. Inhibiting RAC1 in human skin models reduced psoriatic lesions, suggesting RAC1 as a therapeutic target for this inflammatory skin disease.
Area of Science:
- Dermatology
- Immunology
- Molecular Biology
Background:
- Epidermal homeostasis relies on epidermis-immune interactions, which are dysregulated in psoriasis.
- The specific molecular pathways driving aberrant immune responses in psoriatic epidermis remain unclear.
Purpose of the Study:
- To investigate the role of Ras-related C3 botulinum toxin substrate 1 (RAC1) in epidermal dysfunction and psoriasis pathogenesis.
- To explore RAC1 as a potential therapeutic target for psoriasis.
Main Methods:
- Assessed RAC1 activation in psoriatic epidermis and primary human keratinocytes.
- Utilized a mouse model expressing a constitutively active form of RAC1 (RACV12).
- Examined RAC1-dependent signaling and transcriptional changes in human psoriatic skin and xenograft models.
Main Results:
- Elevated RAC1 activation was observed in psoriatic epidermis and keratinocytes.
- RAC1V12 expression in mice induced psoriasis-like lesions dependent on an intact immune system.
- RAC1 modulation affected keratinocyte differentiation, proliferation, and inflammatory pathways (STAT3, NFκB, ZNF750).
- RAC1 inhibition in human xenografts reduced psoriasiform hyperplasia and inflammation.
Conclusions:
- RAC1 is a key mediator of epidermal dysfunction in psoriasis.
- RAC1 plays a critical role in orchestrating pathologic epidermis-immune interactions in psoriasis.
- Targeting RAC1 presents a potential therapeutic strategy for psoriasis.
Related Concept Videos
01:12Renewal of Skin Epidermal Stem Cells
3.2K
The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...
3.2K
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.8K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.8K
01:07MAPK Signaling Cascades
9.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.1K
02:38The Ras Gene
7.5K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
7.5K
01:24T Cell Types and Functions
3.1K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.1K
01:17The Extrinsic Apoptotic Pathway
9.2K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.2K