259 Immunohistochemical insight into the association between the collapse of immune privilege in the sweat gland and syringotropic immune cell infiltrates in collagen diseases

Abstract

The collapse of immune privilege (IP) in the hair follicle (HF) has been implicated in the pathogenesis of autoimmune hair loss disorders. However, whether the sweat gland (SwG) enjoy IP analogous to that of HF remains elusive. In this study, the distribution of IP-related molecules within intact SwG was investigated by a quantitative immunohistochemical approach adopting digital image analysis. Subsequently, the changes in their expression pattern were assessed in lupus erythematosus (LE; n=3), Sjögren syndrome (SjS; n=3), systemic sclerosis/morphea (SSc/morph; n=3) with distinct syringotropic immune cell infiltrates. Similar to HF, normal SwG downregulates MHC class Ia compared to the basal layer of the epidermis. Expression level of MHC class Ia was spatially distinct within SwG; moderate in the ductal portion and most downregulated in the secretory portion (p<0.05). Conversely, immunosuppressive molecules, represented by macrophage migration inhibitory factor (MIF), was most up-regulated in the secretory portion with minimal expression in the basal keratinocytes. Compared to intact SwG, MHC class Ia was markedly upregulated in the ductal portion in LE and the secretory portion in LE, SjS, SSc, preferentially at the sites surrounded by lymphocytic cell infiltration. In contrast, MIF expression level was inversely correlated with the intensity of periglandular cell infiltration. CD200, an immunosupressive HF stem cell marker, was predominantly expressed in myoepithelial cells, putative SwG precursor cells, in normal SwG. Intriguingly, CD200 was mildly downregulated in involved SwG in LE and SjS and markedly suppressed in atrophic SwG in SSc/morph, implying that impaired IP with resultant immunological assault leading to the loss of SwG. These findings suggested that SwG is represents an additional IP site in human skin, and the dysregulation of SwG-IP may contribute to the pathogenesis or pathophysiology of skin diseases affecting SwG.