Skin Commensals and T cells: How Do We Keep the Peace?
Posted 30th December 2016 by Jane Williams
Tiffany Scharschmidt spoke to us about her thoughts on the skin microbiome, immune responses and inflammatory skin diseases.
In my role as a dermatologist, I specialise in the care of patients with severe inflammatory skin disease, and as a physician-scientist, I have combined training in both microbiology and immunology. Both in the clinic and the lab, my passion is to try to understand how our adaptive immune system establishes and maintains a healthy relationship with the commensal bacteria on our skin, and how this symbiosis is altered in inflammatory skin disorders.
Our skin is coated with billions of these healthy non-pathogenic bacteria and contains an equal number of T cells. These T cells protect us from infection by recognising and responding to microbial pathogens. A basic question that drives my work is why does healthy skin show no evidence of inflammation directed against commensal bacteria?
Using a new model to study the CD4 T cell response to a skin commensal bacteria, we recently discovered that exposure to a commensal bacteria during neonatal, but not adult life, leads to immune tolerance. We also identified that an abundant population of activated regulatory T cells (Tregs) enter the skin in neonatal life and mediates this commensal-specific tolerance. Our work is currently focused on dissecting how commensal skin bacteria and molecules facilitate host tolerance.
Inflammatory skin diseases affect billions of people worldwide. I see these patients day in and day out in my clinic and I can tell you these disorders are highly debilitating. Their pathogenesis is clearly complex, but we now recognise that aberrant immune responses to skin bacteria play a central role. It is my hope that our efforts to understand mechanisms that regulate the adaptive immune response to skin commensals will one day translate into a new class of therapeutics that harness microbial molecules to modulate the cutaneous immune response.
I find it deeply gratifying to be able to combine patient care with research pursuits aimed at improving our understanding and treatment of the inflammatory skin diseases from which my patients suffer.
The Changing Field
As a medical student, I worked in the lab of Julie Segre at NHGRI. It was during this period 10 years ago that Julie and her collaborator, Heidi Kong, began studies to characterise the skin microbiome using sequencing techniques. Since then, their groups and others have transformed our understanding of the bacterial, fungal and viral communities that live in healthy and diseased skin. Concurrent work by Yasmine Belkaid’s, Rich Gallo’s and other groups, have begun to functionally dissect the role of these microbes in promoting homeostatic functions of the skin epithelium and skin-resident immune cells.
I view this as a tremendously exciting time to be in the skin microbiome space. Admittedly, we are a decade or so behind the gut microbiome field in our development, but I believe the skin microbiome is of critical importance to health and represents an optimal target for therapeutic intervention. While the last decade of work has focused on identifying who the key microbial players are in the skin, I believe work moving forward will increasingly focus on understanding the role of these microbes in skin health and the mechanisms by which they exert their effects. I look forward to being a part of this exciting effort.
Tiffany Scharschmidt is a dermatologist and physician-scientist at UCSF. In the clinic, she specialises in the care of patients with severe inflammatory skin disease. In the lab, she has combined training in immunology and microbiology.
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