The Skin–Brain Connection Hypothesis, Bringing Together CCL27-Mediated T-Cell Activation in the Skin and Neural Cell Damage in the Adult Brain
Authors: Nataliya L. Blatt, Timur I. Khaiboullin,Vincent C. Lombardi, Albert A. Rizvanov and Svetlana F. Khaiboullina1,
Publication: Front. Immunol., 16 January 2017
Recent discovery of an association of low serum melatonin levels with relapse in multiple sclerosis (MS) opens a new horizon in understanding the pathogenesis of this disease. Skin is the main organ for sensing seasonal changes in duration of sunlight exposure. Level of melatonin production is dependent on light exposure. The molecular mechanisms connecting peripheral (skin) sensing of the light exposure and developing brain inflammation (MS) have not been investigated. We hypothesize that there is a connection between the reaction of skin to seasonal changes in sunlight exposure and the risk of MS and that seasonal changes in light exposure cause peripheral (skin) inflammation, the production of cytokines, and the subsequent inflammation of the brain. In skin of genetically predisposed individuals, cytokines attract memory cutaneous lymphocyte-associated antigen (CLA+) T lymphocytes, which then maintain local inflammation. Once inflammation is resolved, CLA+ lymphocytes return to the circulation, some of which eventually migrate to the brain. Once in the brain these lymphocytes may initiate an inflammatory response. Our observation of increased CC chemokine ligand 27 (CCL27) in MS sera supports the involvement of skin in the pathogenesis of MS. Further, the importance of our data is that CCL27 is a chemokine released by activated keratinocytes, which is upregulated in inflamed skin. We propose that high serum levels of CCL27 in MS are the result of skin inflammation due to exposure to seasonal changes in the sunlight. Future studies will determine whether CCL27 serum level correlates with seasonal changes in sunlight exposure, MS exacerbation, and skin inflammation.
Humoral Immunity Profiling of Subjects with MyalgicEncephalomyelitis Using a Random Peptide MicroarrayDifferentiates Cases from Controls with High Specificityand Sensitivity
Authors: Sahajpreet Singh, Phillip Stafford, Karen A. Schlauch, Richard R. Tillett, Martin Gollery, Stephen Albert Johnston, Svetlana F. Khaiboullina, Kenny L. De Meirleir, Shanti Rawat, Tatjana Mijatovic, Krishnamurthy Subramanian, András Palotás, Vincent C. Lombardi
Publication: Mol Neurobiol (DOI 10.1007/s12035-016-0334-0)
Abstract Myalgic encephalomyelitis (ME) is a complex, heterogeneous illness of unknown etiology. The search for biomarkers that can delineate cases from controls is one of the most active areas of ME research; however, little progress has been made in achieving this goal. In contrast to identifying biomarkers that are directly involved in the pathological process, an immunosignature identifies antibodies raised to proteins expressed during, and potentially involved in, the pathological process. Although these proteins might be unknown, it is possible to detect antibodies that react to these proteins using random peptide arrays. In the present study, we probe a custom 125,000 random 12-mer peptide microarray with sera from 21 ME cases and 21 controls from the USA and Europe and used these data to develop a diagnostic signature. We further used these peptide sequences to potentially uncover the naturally occurring candidate antigens to which these antibodies may specifically react with in vivo. Our analysis revealed a subset of 25 peptides that distinguished cases and controls with high specificity and sensitivity. Additionally, Basic Local Alignment Search Tool (BLAST) searches suggest that these peptides primarily represent human selfantigens and endogenous retroviral sequences and, to a minor extent, viral and bacterial pathogens.
You may have participated in Black Friday and Cyber Monday, today is your chance to participate in #GivingTuesday. This global day of giving reminds us to share our gifts with others in need during the holiday season.
Join the #GivingTuesday movement by giving to Nevada Center for Biomedical Research (NVCBR) in support of local discovery with a global impact. Your tax-deductible donation will help fund our efforts to find answers for millions who suffer from chronic complex neuro-inflammatory diseases, many of whom must live their lives without treatment options.
Donate on our #GivingTuesday donation page or call 775-682-8250 for other donation options. Keep the giving going by sharing your message of giving with your social network by using hashtags #GivingTuesday and #research_nvcbr to encourage friends and family to give as well.
We will accept year-end donations even if it doesn’t fall on #GivingTuesday. Visit the Giving Page on our website or call us for more information about the many ways to give to NVCBR.
Join us on November 29th for #GivingTuesday, a global day dedicated to giving. Following the widely recognized shopping events Black Friday and Cyber Monday, this day of generosity reminds us to share our gifts with others in need during the holiday season.
We encourage you to participate in the #GivingTuesday movement by giving to Nevada Center for Biomedical Research (NVCBR) in support of local discovery with a global impact. Your generous partnership on #GivingTuesday will help fund our efforts to find answers for millions who suffer from chronic complex neuro-inflammatory diseases.
You can easily donate at http://bit.ly/2fWtpbH or call 775-682-8250 for other donation options.
We’re proud to announce that Nevada Center for Biomedical Research will be well represented at the 12th International IACFS/ME Research and Clinical Conference: Emerging Science and Clinical Care in Ft. Lauderdale, FL, from October 27-30, 2016. Dr. Vincent Lombardi, NVCBR Research Director, Dr. Kenny De Meirleir, NVCBR Medical Director, and Annette Whittemore, NVCBR CEO, will attend the biannual conference, as well as the pre-conference at Nova Southeastern University. Drs. De Meirleir and Lombardi will be providing their unique insights into the diagnosis and scientific knowledge of myalgic encephalomyelitis or ME, the International Consensus Committee’s recommended name for this disease. Dr. De Meirleir will be sharing his most current diagnostic protocol, which includes the use of several biomedical tests, to identify those with ME. In addition, Dr. Lombardi will be providing key evidence for the use of a novel set of peptides as biomarkers that can quickly and accurately identify ME patients. This exciting work, which may provide the first specific biomedical biomarker for this disease, as well as direction for future pharmaceutical developments, was recently completed by NVCBR researchers in collaboration with scientists at Arizona State University and the University of Nevada, Reno.
Dr. Lombardi presented at the 2016 American Association of Immunologists annual meeting in Seattle, Washington. Dr. Lombardi presented data supporting a model of gut pathology in ME/CFS whereby dysregulated pDCs fail to promote the production of low-affinity IgA through the process of TI activation of B cells, thereby leading to bacterial overgrowth, dysbiosis, bacterial translocation and systemic immune activation.
- The Skin–Brain Connection Hypothesis, Bringing Together CCL27-Mediated T-Cell Activation in the Skin and Neural Cell Damage in the Adult Brain
- Humoral Immunity Profiling of Subjects with MyalgicEncephalomyelitis Using a Random Peptide MicroarrayDifferentiates Cases from Controls with High Specificityand Sensitivity
- Partner with NVCBR on #GivingTuesday
- Save the Date & Participate! November 29th is #GivingTuesday
- NVCBR Attends 12th International IACFS/ME Research and Clinical Conference