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Article

Molecular Evidence for Precursors of Sjögren’s Foci in Histologically Normal Lacrimal Glands

1
Department of Physiology & Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
2
Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
3
Department of Cell & Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(1), 223; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20010223
Received: 1 November 2018 / Revised: 30 December 2018 / Accepted: 3 January 2019 / Published: 8 January 2019
(This article belongs to the Special Issue Mechanisms of Disease in Sjögren Syndrome)
Understanding the formation of Sjogren’s lymphocytic infiltrates could permit earlier diagnosis and better outcomes. We submitted gene transcript abundances in histologically normal rabbit lacrimal glands to principal component analysis. The analysis identified a cluster of transcripts associated with Sjögren’s foci, including messenger RNAs (mRNAs) for C–X–C motif chemokine ligand 13 (CXCL13) and B-cell activating factor (BAFF), which dominated the major principal component. We interpreted the transcript cluster as the signature of a cluster of integrally functioning cells. Pregnancy and dryness increased the likelihood that the cluster would develop to high levels, but responses were subject to high levels of stochasticity. Analyzing microdissected samples from high- and low-cluster-level glands, we found that certain transcripts, including mRNAs for C–C motif chemokine ligand 21 (CCL21), CXCL13, cluster of differentiation 4 (CD4), CD28, CD25, BAFF, and interleukin 18 (IL-18) were significantly more abundant in immune cell clusters (ICs) from the high-cluster-level gland; mRNAs for CCL2, CD25, and IL-1RA were significantly more abundant in acinus-duct axis samples; mRNAs for CCL4, BAFF, IL-6, and IL-10 were more abundant in some acinus-duct samples; cells with high prolactin immunoreactivity were more frequent in interacinar spaces. In conclusion, integrated functional networks comprising Sjögren’s infiltrates, such as ICs, acinar cells, ductal cells, and interacinar cells, can form in histologically normal glands, and it is feasible to detect their molecular signatures. View Full-Text
Keywords: autoimmunity; lacrimal gland; Sjögren’s syndrome autoimmunity; lacrimal gland; Sjögren’s syndrome
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MDPI and ACS Style

Mircheff, A.K.; Wang, Y.; Pan, B.X.; Parsa, L.; Nandoskar, P.; Ding, C. Molecular Evidence for Precursors of Sjögren’s Foci in Histologically Normal Lacrimal Glands. Int. J. Mol. Sci. 2019, 20, 223. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20010223

AMA Style

Mircheff AK, Wang Y, Pan BX, Parsa L, Nandoskar P, Ding C. Molecular Evidence for Precursors of Sjögren’s Foci in Histologically Normal Lacrimal Glands. International Journal of Molecular Sciences. 2019; 20(1):223. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20010223

Chicago/Turabian Style

Mircheff, Austin K., Yanru Wang, Billy X. Pan, Leili Parsa, Prachi Nandoskar, and Chuanqing Ding. 2019. "Molecular Evidence for Precursors of Sjögren’s Foci in Histologically Normal Lacrimal Glands" International Journal of Molecular Sciences 20, no. 1: 223. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20010223

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