Assessment of tertiary lymphoid structures in salivary glands, pancreas, and lungs of NZB/W lupus prone mice.

Abstract

Autoimmune diseases are complex genetic traits. Factors that trigger autoimmune diseases have yet to be deciphered. It is however suspected that a combination of copious risk factors is implicated in the development of autoimmunity. Genetics, environmental and stochastic factors each contribute to a small degree to the risk of autoimmune disease advancement. SLE is a chronic multisystemic autoimmune disease with various range of clinical manifestations. Autoantibodies are believed to be the primary culprit’ effectors in the development of systemic lupus erythematosus (SLE). SLE is typified by loss of tolerance against nuclear autoantigens, the formation of immune complexes, as well as a multiorgan tissue inflammation. Formation of tertiary lymphoid structure (TLS) emanates in tissue assaulted by chronic inflammatory processes such as infection and autoimmunity. TLS has been observed in almost all organs of the body, these are aggregates of lymphoid and stromal cells that develop at ectopic sites in response to chronic inflammation in autoimmune disease. TLS formation is consociated with tissue damage, indicating that TLSs are paramount regions for self-reactive T- and B-lymphocytes including autoantibody secreting plasma cells that are conducive to the disease state. However, the inaugurating events and signals involved in TLS development and maturation are predominantly unascertained. This study sought to disclose TLS in various tissues of lupus prone NZB/W mice. Immunohistochemistry was used for the detection of TLS in tissues. Immunostaining of formalin-fixed and paraffin-embedded tissues was performed to examine protein expression of CD3 and B220 in the lung, salivary gland, and pancreatic tissue. RNA isolation, reverse transcription, and qPCR was employed to study and evaluate mRNA expression of IL-1ꞵ, IL-18, TNFα, Pigr, Gpr132, Emr4, CD62L(Sell), Gdf3, and Relt in the spleen, lung, and pancreatic tissue. Results illustrated (TLS) occurred predominantly around or adjacent large and small arteries, veins including ducts in the various tissue sample, additionally TLS in pancreatic tissues were detected in Islets of Langerhans. The upregulated genes within the various tissues of lupus prone NZB/W mice established a correspondence between TLS formation and SLE.