Why does hair turn gray? Laurence Meyer, a dermatologist at the University of Utah, offers this explanation: “The pigment in hair, as well as in the skin, is called melanin. There are two types of melanin: eumelanin, which is dark brown or black, and pheomelanin, which is reddish yellow. Both are made by a type of cell called a melanocyte that resides in the hair bulb and along the bottom of the outer layer of skin, or epidermis. The melanocytes pass this pigment to adjoining epidermal cells called keratinocytes, which produce the protein keratinhair’s chief component. When the keratinocytes undergo their scheduled death, they retain the melanin. Thus, the pigment that is visible in the hair and in the skin lies in these dead keratinocyte bodies.” Thus, gray hair is simply hair with less melanin, and white hair has no melanin at all.
During hair growth, melanocytes differentiate from melanocyte stem cells and deposit melanin into the hair shaft. Melanocyte stem cells serve as a reservoir for the production of melanocytes. Studies carried out in mouse models indicate that hair graying is linked to a failure in the maintenance of melanocyte stem cells or in the dysregulated generation of the melanocyte progeny. Now, results from a study published a few months ago in the journal PLOS Biology, suggest a link between hair greying and innate immunity dysregulation.
How are hair greying and innate immunity linked? The answer lies in the melanogenesis associated transcription factor (MITF), which regulates many melanocyte functions. For the study (A direct link between MITF, innate immunity, and hair graying), the researchers used mice that have a predisposition for hair graying. They artificially stimulated the mouse innate immune response, either through a genetic mechanism or via exposure to viral mimic. This artificial stimulation resulted in significant loss of melanocyte stem cell and melanocytes, leading to the increased production of gray hair.
The researchers discovered that MITF has a novel role in the regulation of systemic innate immune gene expression. More specifically, they discovered that MITF is involved in repressing the expression of innate immune genes within cells of the melanocyte lineage by keeping in check interferon responses. Interferons provide signals to other cells—in response to such signals, these cells take action by turning on the expression of genes that inhibit viral replication, activate immune effector cells, and increase host defenses. Notably, the researchers found that the viral mimic poly(I:C) is sufficient to expose genetic susceptibility to hair graying.
Study co-author William Pavan said in a press release: “This new discovery suggests that genes that control pigment in hair and skin also work to control the innate immune system. These results may enhance our understanding of hair graying. More importantly, discovering this connection will help us understand pigmentation diseases with innate immune system involvement like vitiligo.”
One of my students has vitiligo, so that’s something I’ve been trying to learn more about recently. I was excited at the last line of the post saying that the discovery of the virus linked to graying hair has implications for vitiligo. But I was wondering, what else is associated with vitiligo? I know it’s an autoimmune disease, but that’s about all I know as far as how it works. According to one article, vitiligo is associated with elevated levels of memory T cells in the dermis and epidermis. It’s still not clear why this is the case, but it is thought that T resting memory cells are one of the major factors in autoimmune diseases such as vitiligo. The T resting memory cells present in high levels of the skin of vitiligo patients are also associated with with viruses, as they are CD8+, which are the cytotoxic variety of T cells. At this stage, not a lot is known about T resting memory cells, but the authors of the study seem hopeful that they can learn more about them and figure out how to manipulate them in treating autoimmune diseases.
When I was reading through an article about Treg cells, I came across an article that discussed how Treg associated suppressor cytokines (transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) are also thought to be associated with vitiligo. In the study, they found that both TGF-β and IL-10 levels were lower compared to the control. Which makes sense because the other blog post was saying that low Treg cells can cause autoimmune disease. I say this to mean that perhaps more studies regarding T cells, in general, should be looked at in figuring out the pathology to some of these autoimmune diseases.
After reading the blog, I was curious about vitiligo and the new researches made about finding a cure for it. vitiligo is a skin disorder caused primarily by the destruction of melanocytes or the ineffective melanin synthesis pathway. There’s a research that looks at potential anti vitiligo properties of Vernonia anthelmintic plant and the cynarine extracted from its seeds. The seeds have 1,5-Dicaffeoylquinic acid, and its effect on melanin synthesis was studied. The results showed that 1,5-diCQA stimulated an increase of intracellular melanin level and TYR activity without cytotoxicity.
I wanted to learn about what other roles MITF plays in the immune system. As the post states, the study found that MITF promotes melanocyte stem differentiation and hair graying in mice, suggesting that MITF plays a regulatory role in systemic innate immune gene expression. I wondered if any other diseases were related to the regulation of MITF. I was not able to find any study to answer my question, but I found a study which showed that males with higher hair whitening scores was correlated with increased coronary artery calcification and risk of coronary artery disease and other cardiovascular risk factors (CVRFs). The CVRFs they investigated were hypertension, dyslipidemia, diabetes, and smoking. This is interesting to note since coronary artery disease is closely tied to inflammatory response of the immune system. After reading this article, I still wondered if there were any common markers between other diseases and hair graying. Limitations of this study is that only males were evaluated in the study, and the study also noted several other studies which resulted in different findings. Maybe researching more specific markers in the immune system may lead to reproducible results and might also lead to new findings regarding links between the immune system and hair graying mechanisms.
I found your article about hair graying as a visible marker of coronary disease intriguing. It made me wonder if there are other dermatological markers of coronary disease. One hospital-based study showed that men with baldness, thoracic hairiness, and earlobe crease have a 40% prevalence to coronary disease, independent of age. Specifically, they found that parietal (aside from frontal) baldness is associated with increased risk of myocardial infarction, regardless of age and other risk factors. Men with thoracic hairiness displayed a similar risk for myocardial infarction, speculating that possibly testosterone overproduction could also play a role in this association. In addition to the information you have provided, this particular study found that moderate hair graying indicates a risk for myocardial infarction specifically in men under the age of 45. In conclusion, hair graying as well as other dermatological factors has shown to be a visible marker for coronary disease. With the connection between MITF in hair graying and immune cells, I wonder hair graying could potentially be a visible marker for immune-related health conditions as well.
If the innate immune system can affect the color of hair, can it also affect the growth of hair? While attempting to answer this article, I stumbled upon the autoimmune disease Alopecia areata. This disease results in the sudden onset of hair loss. The people that suffer from this disease are generally healthy. It is believed that psychological stress may trigger the disease. It is believed that hair follicles are generally given immune privilege, which is a state in which they are kept secure for immune cells. However, a breech in this immune privilege leads to immune cells clustering around the hair follicle which leads to inflammation and finally hair loss. To treat this scientist have looked into injecting corticosteroids, minoxidil, methotrexate, cyclosporine, and azathioprine. Which are a mixture of steroids, vasodilators, and immune system suppressors. The study showed that all of the substances lead to some regrowth of the hair, but none were truly substantial.
After reading the blog post I was also curious about the relationship between hair and the immune system. It lead me to alopecia areata as well! I found a study that explained and analyzed the immune cells that are present in human hair follicle anagen VI (growth phase). It classified Langerhan cells, CD4+/CD8+ T cells, macrophages, and mast cells as the most prominent cells found around the hair follicle. Langerhan cells and T cells were found to be on the further end of the follicles whilst macrophages and mast cells were found to be in the perifollicular connective tissue. Although these cells are found around the hair follicle, they are not in abundance. This indicates that hair in it’s growth phase has immune privilege and the collapse of this immune privilege can lead to alopecia areata just as you found in your study!
Premature hair graying (PHG) is one of the genetically inherited conditions that some individuals experience at young ages. Besides being a genetically driven condition, PHG is also affected by other environmental factors. These factors include the concentrations of Vitamin D3, Vitamin B12 and Calcium levels in the organism. A study that was conducted in Bengaluru was designed to test the correlation between PHG and levels of these vitamins in individuals with total of 37 cases. According to study outcomes, low levels of Vitamin B12, HDL-C, and serum ferritin have a direct correlation with PHG. However, the study was done among a very small sample and with not diverse demographics. Further studies with diverse and larger samples needed for definite conclusions.
I know that as a person grows older that many of their physiological systems become less and less efficient. This blog post focuses on how grey hairs can indicate less effective innate immune system. It talks about how the molecule MITF is key to this. MITF is a molecule that inhibits the expression of genes that control or influences innate immune system mechanisms. This is seen as more melanocytes begin to become less functional. I started thinking about what other processes can effect and regulate the production of melanocytes from melanocyte stem cells. If we knew what other process affect melanogenesis, then we could target these pathways and maybe control the process of melanogenesis more precisely. This way we can possibly stop the dysfunction of melanocytes, the dysfunction of MITF, and the inhibition of innate immune genes. So, older people would be able to have their innate immune response still be efficient. This is what I think. Here is a paper that goes over a pathway that controls melanogenesis. So I tried to look up any paper that could give me better insight. It focuses on the ERK pathway. ERK is actually the molecule of MAP Kinase. Usually, it is used in signaling cascades and regulate genes in the nucleus. When the ERK pathway is active, it inhibits melanogenesis. The paper also discussed the function of p38. When phosphorylation of p38 occurs, the production of melanin occurs. So, there are pathways that effect melanocyte and melanin production. However, these pathways are used to regulate other cellular mechanisms. It might be difficult to regulate innate immune genes if other mechanism are being downregulated or upregulated as well.
I thought it was interesting that pigmentation in hair was tied to the innate immune system. I also found it interesting that Vitiligo is thought to be associated with the same processes. I found a study which tested dermal sensitivity to allergens in mice both pre and post hair depigmentation. Like humans with Vitiligo, after the mice had lost pigmentation in their hair, they also lost epidermal hypersensitivity to contact allergens. This is likely caused by the decrease in Langerhans Cells associated with depigmentation. Because Langerhans cells are antigen presenting cells, it is likely that their decrease in number is responsible for the lack of hypersensitivity response in patients with compromised skin and hair pigmentation. This supports the theory that hair graying and Vitiligo are associated with each other, and that they are both caused by a deficiency in the immune system.