Two Different Types of Sialoadenitis in the NOD- and MRL/lpr Mouse Models for Sjögren's Syndrome: A Differential Role for Dendritic Cells in the Initiation of Sialoadenitis?

Abstract

SUMMARY: Sjö gren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal glands. In these glands, focal lymphocytic infiltrates develop. Little is known about the initiation of this autoimmune disease. Antigen-presenting cells (APC) such as dendritic cells (DC) can play a role in the initiation of autoimmunity. To date, no data on the presence of DC in Sjö gren's syndrome are available. Several mouse strains, the nonobese diabetic (NOD) and the MRL/lpr mouse, can be used as models for Sjö gren's syndrome. We compared the development of sialoadenitis in the submandibular glands (SMG) of NOD and MRL/lpr mice with particular focus on the presence of APC. DC, macrophages, T cells, and B cells in the SMG were studied by means of immunohistochemistry, after which positively stained cells were quantified. NOD-severe combined immunodeficiency (SCID) mice were used to study the presence of APC in the SMG in the absence of lymphocytes. Before lymphocytic infiltration, increased numbers of DC were detected in the SMG of NOD mice compared with those numbers in control mice and MRL/lpr mice, which suggests that DC play a role in the initiation of sialoadenitis in NOD mice. In the SMG of NOD mice, lymphocytic infiltrates organized in time. In MRL/lpr mice, however, lymphocytic infiltrates were already organized at the time of appearance. This organization was lost over time. In conclusion, two types of sialoadenitis are described in two mouse models for Sjö gren's syndrome. Differences exist with regard to early events that may lead to the development of sialoadenitis and to the composition and organization of inflammatory infiltrates. It is possible that different types of sialoadenitis also exist in humans and that the pathogenetic process in both the early and late phases of the autoimmune reaction differs among patients. (Lab Invest 2000, 80:575-585).

Proapoptosis and Antiapoptosis-Related Molecules During Postnatal Pancreas Development in Control and Nonobese Diabetic Mice: Relationship with Innervation

“…Moreover, Fas, FasL, and Bcl-2 were also more strongly expressed at birth and were localized around ducts and acini. Intriguingly, all these structures resembled nerves, which are known to be present in these exact locations (Kusakabe et al, 1997), as are the first infiltrating antigen-presenting cells (van Blokland et al, 2000), a finding reminiscent of our present data in the pancreas. Moreover, studies on salivary hypofunction in NOD mice showed autoantibodies and T-cell reactivity with neuron-specific reactivity (Esch and Taubman, 1998).…”

Rates of infiltration by macrophages and dendritic cells and expression of interleukin‐18 and interleukin‐12 in the chronic inflammatory lesions of Sjögren's syndrome: Correlation with certain features of immune hyperactivity and factors associated with high risk of lymphoma development

“…In contrast, the implication of IL-18 in lymphomagenesis has not yet been clarified (41,42), and further prospective studies are needed to define the involvement of IL-18-expressing macrophages in the monoclonal B lymphocyte expansions that occur in patients with primary SS. Nevertheless, it may be of relevance that Th2-type cytokine reactions may be induced in vitro and in vivo by IL-18 in the absence of IL-12 (21,43), and such responses have been demonstrated to occur in patients with primary SS, with the intense accumulation of B cells or overt B cell lymphoma in the MSGs (12,44).…”

“…The high expression of APC- derived and APC-recruiting cytokines and chemokines in the inflamed glandular structures of patients with primary SS, as well as in experimental mouse models of SS (35)(36)(37)(38)(39)(40), indirectly implicates APCs in the pathogenesis of SS. In addition, significant infiltration by classic APCs has been reported in the glandular lesions in mouse models of SS, and has been associated with increased expression of Th1-type cytokines and tissue dysfunction (37,41).…”

Professional Antigen Presenting Cells in Minor Salivary Glands in Sjögren's Syndrome: Potential Contribution to the Histopathological Diagnosis?

“…In the MRL/lpr mouse, another mouse model for Sjögren's syndrome (Hoffman et al, 1984), hardly any DC were present before the onset of sialoadenitis (van Blokland et al, 2000). This suggests that DC play an important role in the initiation of sialoadenitis in NOD mice, whereas in MRL/lpr mice their role may be limited.…”