A Potential Role of Type III Interferon in the Glandular Involvement of Sjögren's Syndrome

Tania Mora¹, Felipe Alonso Masso Rojas², Araceli Paez², Mariana Patlan³, Misael Gómez-Mondragón², Alberto Aranda-Frausto⁴, Maya Chacón Pérez⁵ and Luis M. Amezcua-Guerra^6,7, ¹Rheumatology, National Institute of Cardiology, Mexico City, Mexico, ²Department of Cell Physiology, National Institute of Cardiology, Mexico City, Mexico, ³Department of Immunology, National Institute of Cardiology, Mexico City, Mexico, ⁴Department of Pathology, National Institute of Cardiology, Mexico City, Mexico, ⁵National Institute of Cardiology, Mexico City, Mexico, ⁶Immunology, National Institute of Cardiology, Mexico City, Mexico, ⁷Mexican Accreditation Council of Rheumatology, A.C., Mexico City, Mexico

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Sjogren's syndrome and interferons

Session Information

Date: Sunday, November 8, 2015

Title: Sjögren's Syndrome I: Basic Insights

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose:

Primary Sjögren’s syndrome (pSS) is an autoinmune disorder characterized by lymphocytic infiltration of salivary and lachrymal glands. Recently, it has been showed that plasmacytoid dendritic cells (pDC, main cell source of type I IFNs) are reduced in the circulation of pSS patients, although its numbers are substantially increased in the salivary glands. This suggests that pDCs migrate and are housed into the glandular tissue following a specific antigenic stimulus, possibly a viral infection.

Type III IFNs are a novel family of cytokines mainly produced by cytotoxic cells which share many biological activites with type I IFNs. Epithelial tissues are the primary target to IFN-lambda3, which possess the highest activity of all type III IFNs. The possible role that IFN-lambda3 plays in pSS pathogenesis is unknown.

Methods:

Peripheral blood mononuclear cells (PBMC) from patients with pSS and healthy controls were analyzed by conventional flow cytometry to determine the number of T cytotoxic cells (CD8+T cells and CD56+ Natural Killers) that were also positive for IFN-lambda3. In addition, biopsies of minor salivary gland from 6 pSS and 6 non-pSS were evaluated by immunofluorescence with antibodies against CD8, CD56, and IFN-lambda3.

Results:

PBMC from 14 pSS patients and 8 healthy volunteers were included. Flow cytometry counts are presented in the Table.

Cell subtype	pSS (n=14)	Healthy (n=8)	P
CD8+ total cells/1«10⁶ PBMC	104,757 (25,300–226,200)	71,200 (18,600–165,200)	0.3
CD8+IL28+ total cells/1«10⁶ PBMC	1,478 (300–3,700)	2,742 (900–5,900)	0.06
CD8+IL28+ % of total CD8+ cells	1.73% (0.19%–5.9%)	3.96% (2.53%–6.7%)	*0.002*
CD56+ total cells/1«10⁶ PBMC	39,950 (4,500–161,300)	18,085 (11,300–38,800)	0.3
CD56+IL28+ total cells/1«10⁶ PBMC	871 (100–3,100)	2,900 (900–5,300)	*0.009*
CD56+IL28+ % of total CD56+ cells	3.2% (0.43–11.6%)	16% (7.8%–23.7%)	*0.0005*

On immunofluorescence, salivary tissues from pSS patients were extensively infiltrated by CD8+, CD56+, and IFN-lambda3+ cells. As noted, IFN-lambda3+ was in tightly co-localization with both CD8+ and CD56+ cells. This was not noticed in salivary glands from non-pSS individuals.

Conclusion:

The number of circulating cytotoxic cells producing IFN-lambda3 is decreased in the peripheral blood of pSS patients; however, an intense infiltration of cytotoxic cells with high expression of IFN-lambda3 was found in salivary tissue from pSS patients. This suggest the existence of an important stimulus so far unknown (probably a viral infection), causing the migration and homing of cytotoxic cells highly producing IFN-lambda3 from peripheral blood to target tissues.

Bibliography:

Yao Y, et al. Type I interferons in Sjšgren’s syndrome. Autoimmun Rev 2013;12:558-66.

Disclosure: T. Mora, None; F. A. Masso Rojas, None; A. Paez, None; M. Patlan, None; M. Gómez-Mondragón, None; A. Aranda-Frausto, None; M. Chacón Pérez, None; L. M. Amezcua-Guerra, None.

To cite this abstract in AMA style:

Mora T, Masso Rojas FA, Paez A, Patlan M, Gómez-Mondragón M, Aranda-Frausto A, Chacón Pérez M, Amezcua-Guerra LM. A Potential Role of Type III Interferon in the Glandular Involvement of Sjögren’s Syndrome [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/a-potential-role-of-type-iii-interferon-in-the-glandular-involvement-of-sjogrens-syndrome/. Accessed .

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