Liu, Andrew
(2025)
Scratching that Itch: When, how, and why scratching makes your rash worse.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Itch is a dominant symptom in dermatitis and scratching promotes cutaneous inflammation thereby worsening disease. However, the mechanisms through which scratching exacerbates inflammation and whether scratching provides benefit to the host are largely unknown. We now provide a mechanistic underpinning and propose a functional benefit of scratching. While itch-sensing neurons alone are not sufficient to trigger inflammation, we found that itch-sensing neurons and scratching were required for inflammation, mast cell degranulation, and neutrophilic infiltration in the FITC and oxazolone models of CHS, which are Th2 models dependent on IgE/FcεRI. In contrast, itch-sensing neurons and scratching were not required for DNFB-mediated inflammation, a Th1/17 CHS model with no IgE component. Scratching was also required for edematous inflammation in a model of IgE/FcεRI-mediated mast cell activation. In this model, scratching-induced inflammation also required pain-sensing nociceptors, Substance P and MrgprB2. Moreover, direct nociceptor activation rescued scratching-dependent inflammation in collared mice that could not scratch. Scratching also increased mast cell-dependent inflammation and augmented host defense against superficial S. aureus infection. Furthermore, in the context of skin inflammation, scratching also reduced the diversity of the skin microbiome and number of viable skin bacteria. Thus, through activation of nociceptor driven neuroinflammation, scratching both exacerbates allergic skin disease and provides protection from S. aureus, reconciling the seemingly paradoxical role of scratching as a pathological process and evolutionary adaptation.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
14 February 2025 |
| Date Type: |
Publication |
| Defense Date: |
11 December 2024 |
| Approval Date: |
14 February 2025 |
| Submission Date: |
18 December 2024 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
132 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Dermatology
School of Medicine > Immunology
School of Medicine > Neurobiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
When, how, and why scratching makes your rash worse |
| Date Deposited: |
14 Feb 2025 20:35 |
| Last Modified: |
14 Feb 2025 20:35 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/47302 |
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