Role of the Chemokine Receptor CXCR3 in the Function of Regulatory B Cells in Patients with SLE

Shun-ichiro Ota^1,2, Hiroaki Niiro³, Naoko Ueki^2,4, Yuri Hirosaki², Hirofumi Tsuzuki², Siamak Jabbarzadeh-Tabrizi², Tsuyoshi Nakayama², Koji Mishima², Ayako Takaki², Hiroki Mitoma², Mitsuteru Akahoshi², Yojiro Arinobu², Hiroshi Tsukamoto² and Koichi Akashi², ¹Department of Rheumatology, Internal medicine and connective tissue disorders, Shimonoseki City Hospital, Shimonoseki, Japan, ²Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan, ³Clinical Education Center, Kyushu University Hospital, Fukuoka, Japan, ⁴Division of Nephrology and Rheumatology, Fukuoka University, Fukuoka, Japan

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: B cells, Chemokine Receptors, regulatory cells and systemic lupus erythematosus (SLE)

Session Information

Date: Monday, November 9, 2015

Title: B cell Biology and Targets in Rheumatolid Arthritis and other Autoimmune Disease Poster

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: The emerging application of B-cell directed therapies in autoimmune diseases has led to the discovery of a novel B cell population, referred to as regulatory B cells (Bregs), that exerts regulatory functions via IL-10 production. We previously showed that human Bregs are strongly induced in IgM-memory (IgMM) B cell subsets following TLR9 stimulation and Breg functions are impaired due to attenuated induction of Blimp1 in systemic lupus erythematosus (SLE). It remains, however, largely elusive about the underlying mechanisms of this phenomenon in SLE patients. Given a critical role of C-X-C chemokine receptor type 3 (CXCR3) in inflammation, in the present study we have tested whether the migratory potential of Bregs is associated with their regulatory functions in healthy donors and patients with SLE.

Methods: Human B cell subsets in healthy donors and patients with SLE were enriched by cell sorting and subjected to the analysis of gene and protein expression by quantitative PCR, ELISA and flow cytometry.

Results: CXCR3, the chemokine receptor for CXCL10 and CXCL11, is predominantly expressed on T helper type 1 cells, a T-cell subset which plays a pivotal role in the initiation and perpetuation of inflammation. In human B cells CXCR3 was mainly expressed on memory subsets. We first tested Breg potential of CXCR3+ and CXCR3- IgMM B cells in healthy donors, and found that both subsets exhibited comparable potential in IL-10 production, suggesting that CXCR3 expression itself does not affect Breg function. Intriguingly, however, stimulation of CXCL10 and CXCL11 exerted inhibitory and stimulatory effects, respectively, on IL-10 production along with alteration of Blimp1 expression. Consistent with previous findings that the serum levels of CXCL10 are elevated in patients with SLE, CXCR3+ IgMM B cells in patients exhibited decreased potential in IL-10 expression compared with this subset in healthy donors, suggesting that aberrant expression of chemokine ligands is associated with crippled Breg function in patients with SLE.

Conclusion: Together, these findings uncover not only a new aspect of regulation of Breg function in humans, but also a novel clue to the revitalization of Bregs for the treatment of SLE.

Disclosure: S. I. Ota, None; H. Niiro, None; N. Ueki, None; Y. Hirosaki, None; H. Tsuzuki, None; S. Jabbarzadeh-Tabrizi, None; T. Nakayama, None; K. Mishima, None; A. Takaki, None; H. Mitoma, None; M. Akahoshi, None; Y. Arinobu, None; H. Tsukamoto, None; K. Akashi, None.

To cite this abstract in AMA style:

Ota SI, Niiro H, Ueki N, Hirosaki Y, Tsuzuki H, Jabbarzadeh-Tabrizi S, Nakayama T, Mishima K, Takaki A, Mitoma H, Akahoshi M, Arinobu Y, Tsukamoto H, Akashi K. Role of the Chemokine Receptor CXCR3 in the Function of Regulatory B Cells in Patients with SLE [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/role-of-the-chemokine-receptor-cxcr3-in-the-function-of-regulatory-b-cells-in-patients-with-sle/. Accessed .

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