Invariant natural killer T cells are reduced in peripheral blood of bullous pemphigoid patients and accumulate in lesion
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Invariant natural killer T cells are reduced in peripheral blood of bullous pemphigoid patients and accumulate in lesional skin Linda M. Mathias1 · Miriam Harff1 · Valerie Orth2 · Silke C. Hofmann1 Received: 27 July 2019 / Revised: 22 November 2019 / Accepted: 11 December 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019
Abstract iNKT (invariant natural killer T) cells are unconventional immunoregulatory T cells which contribute to B cell maturation, antibody and cytokine production. iNKT cells are implicated in the control of autoimmune inflammation in different disorders. For bullous pemphigoid (BP), the most frequent bullous autoimmune dermatosis, the role of iNKT cells has not yet been studied. We, therefore, aimed at investigating the frequency of iNKT cells in peripheral blood and biopsies from lesional and non-lesional skin from patients with BP and controls. Circulating C D3+iTCR+ iNKT cells were assessed by flow cytometry in peripheral blood from 30 patients with BP and from 29 controls (19 patients with skin tumors and 10 healthy controls). In 34 lesional and 13 non-lesional skin biopsies from BP patients and 17 biopsies from control individuals the number of Vα24+Vβ11+ iNKT cells was investigated by immunofluorescence staining. BP patients showed a significantly lower frequency of circulating iNKT cells compared to the control group. Patients with severe disseminated blistering tended to display lower iNKT cell numbers than patients with moderate disease severity. In lesional skin of BP patients, an enrichment of iNKT cells was detected compared to skin biopsies from controls. Similarly to control biopsies, non-lesional biopsies of BP patients contained only few iNKT cells. In conclusion, the deficiency of circulating iNKT cells associated with enrichment at the site of cutaneous inflammation suggests that iNKT cells may play a pathophysiologically relevant role in BP. Keywords Autoantibody · Flow cytometry · Hemidesmosome · Immunofluorescence · Invariant natural killer T cells
Background Bullous pemphigoid (BP) is the most common bullous autoimmune dermatosis. It occurs mainly in elderly people and due to demographic changes the incidence of BP has steadily increased in the last decades [16]. Clinically, BP is characterized by pruritic eczematous, urticarial or bullous skin alterations associated with tissue-bound and circulating autoantibodies against hemidesmosomal proteins (BP 180 and/or BP 230) [10]. Linda M. Mathias and Miriam Harff contributed equally. * Silke C. Hofmann silke.hofmann@helios‑gesundheit.de 1
Department of Dermatology, Allergology and Dermatosurgery, HELIOS University Hospital Wuppertal, University Witten/Herdecke, Heusnerstr. 40, 42283 Wuppertal, Germany
Department of Surgery, HELIOS University Hospital Wuppertal, University Witten/Herdecke, Wuppertal, Germany
2
Although autoantibodies play a key role in BP, T cell help is required for pathogenic autoantibody production. The innate immune system contributes to inducing dermo-e
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