T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives.

Giuseppe Banfi,Paolo D Pigatto,Eva Reali,Marco Diani

doi:10.3390/ijms21041186

Abstract

Fibromyalgia is one of the most important “rheumatic” disorders, after osteoarthritis. The etiology of the disease is still not clear. At the moment, the most defined pathological mechanism is the alteration of central pain pathways, and emotional conditions can trigger or worsen symptoms. Increasing evidence supports the role of mast cells in maintaining pain conditions such as musculoskeletal pain and central sensitization. Importantly, mast cells can mediate microglia activation through the production of proinflammatory cytokines such as IL-1β, IL-6, and TNFα. In addition, levels of chemokines and proinflammatory cytokines are enhanced in serum and could contribute to inflammation at systemic level. Despite the well-characterized relationship between the nervous system and inflammation, the mechanism that links the different pathological features of fibromyalgia, including stress-related manifestations, central sensitization, and dysregulation of the innate and adaptive immune responses is largely unknown. This review aims to provide an overview of the current understanding of the role of adaptive immune cells, in particular T cells, in the physiopathology of fibromyalgia. It also aims at linking the latest advances emerging from basic science to envisage new perspectives to explain the role of T cells in interconnecting the psychological, neurological, and inflammatory symptoms of fibromyalgia.

Highlights

Fibromyalgia often comes to the attention of the orthopedic clinics because of the widespread chronic pain and musculoskeletal symptoms such as back and neck pain
The results indicated that the number of CD3+T cells expressing the activation markers CD69 and CD25 was decreased in patients with fibromyalgia, whereas the CD4/CD8 ratio was similar in patients and controls. [61]
Analysis of literature data provides non-conclusive results on the role of T cells in the development and maintenance of fibromyalgia symptoms. It emerges that in most cases, altered frequency and/or polarization of T cells mainly in the CD4+ T cell compartment is observed in patients

Summary

Background

Fibromyalgia often comes to the attention of the orthopedic clinics because of the widespread chronic pain and musculoskeletal symptoms such as back and neck pain. Microglia, through these mechanisms, can contribute to brain inflammation and to the pathogenesis of different brain disorders [41,47,48,49,50,51,52] Together these studies underline the role of cells and mediators of the innate immunity in maintaining pain conditions such as musculoskeletal pain and central sensitization [53]. It is, important to note that a very novel finding in the transgenic experimental mouse model showed that nociceptor stimulation of peripheral sensory afferent neurons was able to induce IL-17 secretion by local TCRγδ T cells and by CD4+ T cells [54]. Despite the increasing evidence in this field, the interconnections between the main symptoms of fibromyalgia, such as stress, anxiety, chronic musculoskeletal pain, and the adaptive immune responses still need an explanation

Literature Data

T Cell Mediated Immune Response in Fibromyalgia

Concluding Remarks