Daniele Mauro1,2, Federica Macaluso1,2, Serena Fasano1, Riccardo Alessandro3, Francesco Ciccia4. 1. Dipartimento di Medicina di Precisione, Section of Rheumatology, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy. 2. Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), Università degli Studi di Palermo, Palermo, Italy. 3. Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy. 4. Dipartimento di Medicina di Precisione, Section of Rheumatology, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy. francesco.ciccia@unicampania.it.
Abstract
PURPOSE OF REVIEW: A growing body of evidence supports the relevance of the interleukin-23/interleukin-17 (IL-23/IL-17) pathway for the pathogenesis of axial spondyloarthritis (axSpA) and its treatment. Recently, innate lymphoid cells (ILC), a heterogeneous family of immune effector cells, have been identified as a relevant contributor in tissue homeostasis, partially via IL-23/IL-17 axis. This review describes the biology and the origins of the group 3 ILCs (ILC3s) in humans, focusing on their role in the pathogenesis of axSpA. RECENT FINDINGS: Clinical trials showed the effectiveness of IL23/IL-17 axis inhibition in both spondyloarthritis (SpA) and Inflammatory Bowel Disease (IBD). Recent findings confirm the high prevalence of subclinical gut inflammation in patients with SpA. Translational data in humans have demonstrated an increase in the number of ILC3s responsive to IL-23 and producing either IL-22 or IL-17 in the gut of SpA patients. The observation of gut-derived ILC3s in circulation and at inflamed tissues in patients with SpA suggest a recirculation of ILCs from mucosal site to lymphoid tissues and possibly enthesis and joints. Multiple observations demonstrate the expansion of IL-17- and IL-22-producing ILC3 in the subclinically inflamed gut of SpA patients. These innate immune cells, also observed in normal entheses, seem to be able to re-circulate from the gut to inflamed tissues of SpA patients, thus contributing to the disease perpetuation. The development of tools that can provide access to diseased tissue from sacroiliac joint and spinal entheses will provide valuable knowledge on the role of ILC3 in axSpA pathogenesis.
PURPOSE OF REVIEW: A growing body of evidence supports the relevance of the interleukin-23/interleukin-17 (IL-23/IL-17) pathway for the pathogenesis of axial spondyloarthritis (axSpA) and its treatment. Recently, innate lymphoid cells (ILC), a heterogeneous family of immune effector cells, have been identified as a relevant contributor in tissue homeostasis, partially via IL-23/IL-17 axis. This review describes the biology and the origins of the group 3 ILCs (ILC3s) in humans, focusing on their role in the pathogenesis of axSpA. RECENT FINDINGS: Clinical trials showed the effectiveness of IL23/IL-17 axis inhibition in both spondyloarthritis (SpA) and Inflammatory Bowel Disease (IBD). Recent findings confirm the high prevalence of subclinical gut inflammation in patients with SpA. Translational data in humans have demonstrated an increase in the number of ILC3s responsive to IL-23 and producing either IL-22 or IL-17 in the gut of SpA patients. The observation of gut-derived ILC3s in circulation and at inflamed tissues in patients with SpA suggest a recirculation of ILCs from mucosal site to lymphoid tissues and possibly enthesis and joints. Multiple observations demonstrate the expansion of IL-17- and IL-22-producing ILC3 in the subclinically inflamed gut of SpA patients. These innate immune cells, also observed in normal entheses, seem to be able to re-circulate from the gut to inflamed tissues of SpA patients, thus contributing to the disease perpetuation. The development of tools that can provide access to diseased tissue from sacroiliac joint and spinal entheses will provide valuable knowledge on the role of ILC3 in axSpA pathogenesis.
Entities:
Keywords:
Ankylosing spondylitis; Group 3 innate lymphoid cells; Gut inflammation; IL-17; IL-23/IL-17 axis; Lymphoid tissue inducer cells; Spondyloarthritis
Authors: Meike Wendland; Niklas Czeloth; Nicolas Mach; Bernard Malissen; Elisabeth Kremmer; Oliver Pabst; Reinhold Förster Journal: Proc Natl Acad Sci U S A Date: 2007-04-02 Impact factor: 11.205
Authors: Ivaylo I Ivanov; Brent S McKenzie; Liang Zhou; Carlos E Tadokoro; Alice Lepelley; Juan J Lafaille; Daniel J Cua; Dan R Littman Journal: Cell Date: 2006-09-22 Impact factor: 41.582
Authors: Tom Cupedo; Natasha K Crellin; Natalie Papazian; Elwin J Rombouts; Kees Weijer; Jane L Grogan; Willem E Fibbe; Jan J Cornelissen; Hergen Spits Journal: Nat Immunol Date: 2008-11-23 Impact factor: 25.606
Authors: Yan Zheng; Patricia A Valdez; Dimitry M Danilenko; Yan Hu; Susan M Sa; Qian Gong; Alexander R Abbas; Zora Modrusan; Nico Ghilardi; Frederic J de Sauvage; Wenjun Ouyang Journal: Nat Med Date: 2008-02-10 Impact factor: 53.440