Immunoporosis: Immunology of Osteoporosis-Role of T Cells

Abstract

The role of immune system in various bone pathologies, such as osteoporosis, osteoarthritis, and rheumatoid arthritis is now well established. This had led to the emergence of a modern field of systems biology called as osteoimmunology, an integrated research between fields of immunology and bone biology under one umbrella. Osteoporosis is one of the most common inflammatory bone loss condition with more than 200 million individuals affected worldwide. T helper (Th) cells along with various other immune cells are major players involved in bone homeostasis. In the present review, we specifically discuss the role of various defined T lymphocyte subsets (Th cells comprising Th1, Th2, Th9, Th17, Th22, regulatory T cells, follicular helper T cells, natural killer T cells, γδ T cells, and CD8⁺ T cells) in the pathophysiology of osteoporosis. The study of the specific role of immune system in osteoporosis has now been proposed by our group as "immunoporosis: the immunology of osteoporosis" with special emphasis on the role of various subsets of T lymphocytes. The establishment of this new field had been need of the hour due to the emergence of novel roles of various T cell lymphocytes in accelerated bone loss observed during osteoporosis. Activated T cells either directly or indirectly through the secretion of various cytokines and factors modulate bone health and thereby regulate bone remodeling. Several studies have summarized the role of inflammation in pathogenesis of osteoporosis but very few reports had delineated the precise role of various T cell subsets in the pathobiology of osteoporosis. The present review thus for the first time clearly highlights and summarizes the role of various T lymphocytes in the development and pathophysiology of osteoporosis, giving birth to a new field of biology termed as "immunoporosis". This novel field will thus provide an overview of the nexus between the cellular components of both bone and immune systems, responsible for the observed bone loss in osteoporosis. A molecular insight into the upcoming and novel field of immunoporosis would thus leads to development of innovative approaches for the prevention and treatment of osteoporosis.

Keywords: T lymphocytes; bone loss; immunoporosis; osteoimmunology; osteoporosis.

Figure 1

Bone remodelling. Bone undergoes continuous remodelling as a result of interaction between bone-forming osteoblasts and bone-resorbing osteoclasts. Both osteoclasts and osteoblasts lead to fine tuning of osteocytes, which in turn modulates remodelling. Osteoblasts are derivatives of MSCs and produce extracellular bone matrix of type I collagen and non-collagenous proteins, including osteocalcin, osteonectin, and osteopontin. Multinucleated osteoclasts are produced as a result of differentiation of macrophages and monocytes. RANKL in the presence of MCSF is primarily responsible for functioning and activation of osteoclasts leading to bone loss. On the other hand, osteoblasts produce OPG, which inhibits bone loss by inhibiting osteoclastogenesis. MSC, Mesenchymal stem cell; HSC, Hematopoietic stem cell; RANKL, Receptor activator for nuclear factor kappa; OPG, Osteoprotegerin.

Figure 2

Diversity of T helper (Th) cells. The signature cytokines produced by respective Th cells are shown along with their immunomodulatory properties in boxes. STAT, Signal transducer and activator of transcription; RORγ, RAR-related orphan receptor gamma; Foxp3, Forkhead box P3; BCL6, B-cell lymphoma 6.

Figure 3

Role of T cells in Immunoporosis. T cells, including the T helper (Th) cells, cytotoxic T cells have pivotal role in the induction of osteoporosis-associated bone loss. Within T helper (Th) cells, Th9 cells, Th17 cells, NK T cells, and follicular helper T (T_FH) cells have been reported to enhance bone loss in osteoporosis. On the other hand, Th1, Th2, Tregs, and CD8T cells have been associated with osteoprotective properties, thereby inhibiting osteoporosis. The role of γδ T cells need more studies to relate them with osteoporosis.