No Hair Works Alone—Hair Plucking and Growth

Image of woman plucking eyebrow with tweezer

Plucking of mouse hair is often used in the laboratory to investigate the hair cycle and sometimes to remove the pelage covering the skin before applying chemicals, drugs, ultraviolet irradiation or other components of the experimental tool box. An article by a cross-disciplinary team composed of dermatologists, stem cell biologists, developmental biologists, immunologists, mathematical biologists, and tissue engineers have worked together from diverse regions including the US, Taiwan, People’s Republic of China, and the UK. The result is a stimulating article in CELL about a simple principle underlying the population regenerative behavior in a complex biological system (Chen et al., 2015).

Important points:

  • Plucking hairs stimulate regeneration of both plucked follicles and unplucked adjacent follicles at some distance by some signals sent out from plucked follicles.
  • The immune system plays an essential role in this regenerative process. Hair follicles produce proinflammatory cytokines, including the chemokine CCL2, which attracts inflammatory macrophages with tumor necrosis factor alpha. These macrophages are necessary for spreading the signal afar, achieving the two-step signaling propagation.
  • Mathematical modeling of this system is consistent with the process of quorum sensing. Quorum sensing behaviors are often seen in bacteria and social insects such as ants and bees. Here, hair regeneration is shown as an interesting and important quorum phenomena in a mammalian system. “Quorum” in such systems describes a condition in which numbers of individual cells, organisms, or organs (e.g., hair follicles) are necessary for a change rather than an absolute level of chemical mediator.
  • NF-kappa B is one of the important mediators that stimulate hair regeneration.
  • In addition to the detailed mechanism that functions after hair plucking, this article shows that mathematical modeling analyses can helps to reveal a deeper level of understanding of skin diseases.
  • The institutional origin of the investigators is a perfect demonstration of the importance of involving multiple disciplines in research, as well as the broad international nature of skin-related and all research.
  • As investigators use wax or plucking to remove hairs to study their own hypotheses, they must be cognizant of all the quorum processes going on beneath the skin surface.
  • Hair disorders and organs beyond the skin may be co-opting the evolutionarily conserved quorum sensing principles for health or disease.

References        

Chen et al (2015) Organ-level quorum sensing directs regeneration in hair stem cell populations. Cell 161:277-290

Editors’ Picks from Experimental Dermatology

Epidermal suction blister gene expression study suggests an influence of non pigmentary genes for the regulation of ethnic skin color

Differences in visible skin pigmentation are a major determinant of skin color associated with ethnic background. The initial goal of this study (Yin et al, 2014) performed on epidermal extracts from individuals of Caucasian, Asian, and African ancestry, was to identify differentially expressed genes with a special focus on known pigment-related genes. However, only a few of them were found to be significantly differently expressed, such as FRZB, CDH12, SOX5 and KITLG. The major result was that the skin of Caucasians and Asians had highly similar gene expression patterns that differed significantly from the pattern of African skin. Interestingly, ADRA2C (α-2C adrenergic receptor) had a high expression level in African skin but low expression levels in Asian and Caucasian skin. α2-adrenoceptors are G-protein-coupled receptors that mediate many of the physiological effects of norepinephrine and epinephrine and they can regulate skin color in zebrafish (Ruuskanen et al, 2005). In humans, their so far unsuspected role in the regulation of pigmentation needs further investigation. NINL was found to be expressed at a significantly different level in Caucasian and Asian skin, in which comparable melanocyte populations and very similar melanin contents have been found. NINL has been shown to be involved in microtubule organization, and high levels of NINL expression cause lysosomes to disperse towards the cell periphery (Casenghi et al, 2005). Since melanosomes are lysosome-related organelles and their distribution is regulated by various cytoskeletal components, including microtubules, the authors hypothesize that the higher expression level of NINL in Asian skin might play a critical role in the different distribution patterns of melanosomes that result in visible skin color differences

Submitted by Alain Taieb, Bordeaux, France

References:

Yin L et al  (2014) Epidermal gene expression and ethnic pigmentation variations among individuals of Asian, European and African ancestry. Exp Dermatol. Oct;23(10):731-5. doi: 10.1111/exd.12518

Ruuskanen JO, Peitsaro N, Kaslin JV et al. J Neurochem 2005; 94: 1559-1569.

Casenghi M, Barr FA, Nigg EA. J Cell Sci 2005; 118: 5101-5108.

 

Bypassing epidermal immunity: A case of soft tissue infection in psoriatic skin

Psoriatic skin is characterized by an enhanced protective epidermal shield of antimicrobial peptides and proteins (AMPs). It is commonly believed that enhanced AMP levels in the skin from psoriasis patients, in contrast to those of atopic dermatitis patients, confer resistance to skin infections (Gambichlet et al, 2008; Ong et al, 2002; Howell et al, 2006).  However, if bypassed through penetrating injuries, epidermal AMPs are not sufficient to protect from bacterial soft tissue infection, as reported by Steinz et al (2014). This clinical observation goes against the paradigm that AMPs provide antimicrobial resistance and highlights that the route of infection and not local AMP deficiency may contribute to disturbed skin immunity. In addition, it remains to be determined whether topical psoriasis treatments, such as vitamin D derivatives or steroids, may inhibit the cutaneous immune system, resulting in enhanced infection susceptibility.

Submitted by Amanda S. MacLeod, Durham, NC, USA

References:

Gambichler T, Skrygan M, Tomi NS, Othlinghaus N, Brockmeyer NH, Altmeyer P, Kreuter A. (2008) Differential mRNA expression of antimicrobial peptides and proteins in atopic dermatitis as compared to psoriasis vulgaris and healthy skin. Int Arch Allergy Immunol. 47(1):17-24.

Ong PY1, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY (2002) Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 10:347(15):1151-60.

Howell MD, Gallo RL, Boguniewicz M, Jones JF, Wong C, Streib JE, Leung DY (2006) Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity 24(3):341-8.

Steinz K, Schubert S, Harder J, Gerdes S, Mrowietz U, Gläser R. (2014) Bacterial soft tissue infection in psoriasis despite induction of epidermal antimicrobial peptides. Exp Dermatol. 23(11):862-4

 

Stress and itch: Understanding the psychological aspects is important

The main complaint of patients suffering of atopic dermatitis is itch. Stress is understood to diminish the perception threshold of itch in this and many other diseases. However, it remained unclear which factors could explain this relationship.

Schut et al. wondered if certain coping strategies could be activated under stress. Coping can be defined as adaptable thoughts and behaviors intended to manage subjective demanding experiences. They investigated the role of coping as a possible mediating factor between stress and itch in patients with atopic dermatitis. Coping and itch were assessed by self-report measures, while stress was not only measured by a validated questionnaire, but also by a physiological stress marker, the post-awakening level of cortisol. Using a regression- and a mediation analysis, this study showed a relationship between perceived stress and itch, which was fully mediated by negative itch-related cognitions. More than 62% of the variance of itch intensity could be explained by negative itch-related cognitions.

These findings help to explain the positive effects of cognitive restructuring in the treatment of chronic itch. They provide a further scientific rationale for cognitive restructuring in the treatment of atopic dermatitis.

Submitted by Laurent Misery, Brest, France

Reference:

Schut C, Wiek U, Tews N, Gieler U, Deinzer R, Kupfer J. (2015) Coping as mediator of the relationship between stress and itch in patients with atopic dermatitis: a regression- and mediation analysis. Exp Dermatol 24(2):148-50

 

Hair Follicles’ Promise in Wound Healing

Jimenez et al.’s interesting essay, “Reflections on how wound healing-promoting effects of the hair follicle can be translated into clinical practice,” reviews experimental and clinical evidence regarding the potential benefits of using hair follicles in wound healing, and possible common pathways with hair cycling, including the role of molecular and cellular mechanisms.

The authors provide examples of the use of hair-related therapies to manage chronic wounds, such as cultured epidermal autografts obtained from the outer root sheath, and hair-bearing donor skin. Although the essay focuses on the influence of hair biology in wound healing, the points discussed are also applicable to therapies for depigmenting disorders and hair neogenesis for cicatricial alopecias, among others.

While the clinical evidence is still preliminary, in our opinion further research in hair biology may provide greatly needed new and effective wound healing therapies.

Submitted by Katherine L. Baquerizo Nole and Robert S. Kirsner, University of Miami, Miami, Florida, USA

References:

Jimenez F, Poblet E, Izeta A. (2015) Reflections on how wound healing-promoting effects of the hair follicle can be translated into clinical practice. Exp Dermatol  24(2):91-4.

Wringing Warts Till They Blister

Image credit: TInus Beyers / Shutterstock.com

For over two thousand years blistering beetles and their extracts have been used to remove noxious, noisome, persistent warts from skin. Research through 1960 (yes, before many of us were born), before keratinocyte culture, before PCR, before demonstrating autoantibodies in Pemphigus and Pemphigoid, was reviewed and worth a read, since it may yield clues pertinent even today (Bagatell & Stoughton, 1964).

Fast forward to last month.

At the Society for Investigative Dermatology meeting in Atlanta in May 2015, Li et al reported fascinating research in cultured human keratinocytes. Cantharidin, the active blistering component of blister beetle juice, specifically cleaved desmocollin (DSC) 2/3 both extracellularly and intracellularly, and DSC ectodomain fragments appeared in the culture media.. Even more interesting was that cantharidin caused intracellular cleavage of DSC . The extracellular cleavage was blocked by metalloprotease inhibitors, and a tyrosine kinase inhibitor, genistin, blocked both the extracellular and intracellular cleavage of DSC 2/3. Those interested in tyrosine kinases may let their imaginations run wild concerning new wart therapies.

Another major question beyond these very interesting mechanistic findings is whether the mechanism of acantholysis caused by cantharidin is a clue to the mechanism of acantholysis in some of the autoimmune blistering diseases.

 

References

Bagatell, F and Stoughton RB (1964) Vesication and Acantholysis chapter XXXI, in The Epidermis W. Montagna and WC Lobitz eds. Academic Press, NY, NY, pages 601-611.

Li, N, Liu, Z, Diaz, LA (2015) Desmocollin ectodomain shedding and cantharidin acantholysis Abstract Number 382, J Invest Derm 135:S65, 2015, page S65 (Abstract Number 382).

 

Conflict of Interest:

Your blogger in an Emeritus professor at UNC Chapel Hill where this research was conducted but had no role in the research.

Disney Is Correct: It Is a Small World for . . . Investigating Psoriasis

Christopher Griffiths, Head of Dermatology at the University of Manchester in the UK gave the plenary Eugene Farber lecture on “The Natural History of Psoriasis” at the Society for Investigative Dermatology annual meeting on May 7, 2015 in Atlanta, Georgia. I was stimulated in many dimensions:  by the excellent research and presentation style, the wonderful use of the King’s/Queen’s English, and the incredible organization of the UK Dermatology enterprise in generating and sharing data.

The English dermatologists have developed nationwide organizations for collecting, analyzing, and disseminating important clinical data. A little investigation showed that dermatologists around the world are contributing to similar big data sets for the benefit of patients.

Examples are within an alphabet soup of acronyms; it should be noted that the BAD, the British Association of Dermatologists, is a key mover in this process. UK-TREND (UK Translational Research Network in Dermatology), a membership organization started in 2013, is one example of the BAD’s commitment to facilitating translational research in skin biology and disease to improve patient care.-

 

image credit: www.shutterstock.com / 903418000Other examples include:

BADBIR – British Association of Dermatologists Biologic Interventions Register

BADGEM – British Association of Dermatologists Dermatology and Genetic Medicine

PSORT –  Psoriasis stratification to optimize relevant therapy

 

Another international group collecting data, including data on adverse events is:

PSOLAR – (Psoriasis Longitudinal Assessment and Registry) is a multinational group of investigators collecting important data on longitudinal fashion on now over 1,496 patients (Kalb et al, 2015) in the US (74.3%), Canada (13.7%), and the rest in other regions of the world.

 

All of these groups address important research and clinical issues, and several have industry support.

Data from these groups will lead to relevant information for patient management.. The stratification studies can also lead to choosing between apparently equivalent therapies that may be more beneficial for one subset of patients compared with others.

 

REFERENCE:

RE Kalb, DF Fiorentino, MG Lebwohl, et al (2015) Risk of serious infection with biologic and systemic treatment for psoriasis. JAMA Dermatology   doi: 10.1001/jamaddermatol.2015.0718