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Dr. Rupesh K. Srivastava

PhD, MBA

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Welcome to Translational Immunology, Osteoimmunology & Immunoporosis Lab group at AIIMS, New Delhi. During my doctoral research work form NCCS, Pune I got a glimpse of the very exciting and thrilling field of Immunology. This led me to further continue my research work in the field of Bone and Immunology at Columbia University Medical Centre, NY, USA and Roswell Park Cancer Institute (RPCI), New York, USA. After coming back to India in 2013 as an Assistant professor at Central University, Sagar (MP), and now at All India Institute of Medical Sciences (AIIMS), New Delhi, I am actively involved in deciphering this new field which is still in its very naive state. My research specifically focuses on the cellular and molecular interactions between the Immune and Bone systems i.e “Osteoimmunology” (Frontiers in Biosciences, 2018), a very recent branch of modern biology which specifically deals with the interplay between the immune cells (CD4, CD8 T cells, B cells, DCs, Macrophages, ILCs etc.) and bone cells (Osteoclast, Osteoblast & Osteocytes). During normal physiology both systems are at homeostasis but during an imbalance due to various stimuli (infection, autoimmunity, environment, ageing, hormones etc.), it leads to various inflammatory conditions such as Osteoarthritis, Rheumatoid Arthritis & Osteoporosis (viz. post-menopausal osteoporosis). Thus, a molecular understanding of these interactions is at the heart of my research which would ultimately lead to discovery of novel therapeutics for various inflammatory bone conditions.

My Lab is currently involved in the following areas of  "Translational Medical Research":

Vision: By bridging immunology, microbiology, metabolism, environmental health, &computational biology, my group is pioneering several novel disciplines—Immunoporosis, Osteomicrobiology, OsteoBiotics, Osteometabolism, Osteotoxicology, and Osteofertility. Our translational vision is to translate basic discoveries into safe, immune-modulating, and microbiota-based therapeutics for osteoporosis, osteoarthritis, fractures, and other bone pathologies affecting millions worldwide.

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KEY CONTRIBUTIONS & RESEARCH THEMES

I. “Immunoporosis”: Immunopathophysiology of Osteoporosis

We are pioneers in discovering & defining the immune system’s critical role in osteoporosis pathogenesis, coining the term “Immunoporosis” (Front. Immunol., 2018; PNAS-India, 2021; J. of Inflammation Research, 2022; Intech Open, 2024). This framework highlights how both innate and adaptive immune responses drive bone fragility, opening new avenues for immune-based therapies.

II. Discovering novel roles of Immune Cells in Bone Homeostasis

  • Bregs: We discovered the anti-osteoclastogenic role of regulatory B cells, inhibiting osteoclastogenesis in an IL–10–dependent manner (BBA, 2024; Front. Immunol., 2021).​

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  • Th9 cells: We discovered the osteoclastogenic role of Th9 cells in an IL-9-dependent manner, identifying them as the 2nd osteoclastogenic Th-cell subset (after Th17) (JBMR Plus, 2024).

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  • GTregs: We identified gut-resident Tregs as bone-protective, promoting osteoblast activity and limiting osteoclastogenesis. Their disruption by SCFA deficiency accelerates bone loss, while probiotic supplementation restores their function (J. Leukocyte Biol., 2025).

III. “Gut–Immune–Bone” & “Breg-Treg Vs Th9-Th17” Cell Axis

Our studies established that dysbiosis-induced leaky gut exacerbates postmenopausal osteoporosis (PMO). Estrogen deficiency shifts microbiota composition, increasing endotoxin-producing and reducing SCFA-producing bacteria, thereby worsening inflammatory bone loss. Importantly, we showed that probiotics like Bacillus coagulans restore microbial balance, enhance Breg-Treg functions along with dampening Th9-Th17 cell responses, and improve bone density and strength (Gut Microbes, 2025). This work has established the therapeutic potential of the “Gut–Immune–Bone” axis, which targets and establishes the Therapeutic “Breg-Treg Vs Th9-Th17” cell axis.

IV. Pioneered multiple novel Interdisciplinary fields in Bone Health

  • Osteomicrobiology/Osteobiotics: Uncovering how probiotics and Gut-Associated Metabolites-GAMs (SCFAs, indole derivatives, bile acids, etc.) regulate skeletal health (Bone Reports, 2018; Nutrition, 2018; Scientific Reports, 2021; Front. Immunol., 2022; Front. Microbiol., 2022, J. of Biological Macromolecules, 2024).

 

  • Osteometabolism: Introducing the concept of skeletal cell bioenergetics in bone remodelling and identifying GAMs as regulators of osteoblast/osteoclast energetics (Cells, 2022). Our data suggest probiotics and dietary interventions as safe, accessible therapies for osteoporosis, RA, and other metabolic bone diseases.

 

  • Osteo-Therapeutics: We have systematically evaluated phytoconstituents and Ayurvedic plants (Cissus quadrangularis-HADJOD, Moringa oleifera-DRUM STICK, Crocus sativus-SAFFRON), demonstrating their anti-osteoporotic potential (Cells, 2023; Phytomedicine Plus, 2022). Our group is also conducting scientifically rigorous evaluations of various homoeopathic formulations (MoU with CCRH), addressing a major knowledge gap in alternative therapeutics for bone health.

V. Environmental and Lifestyle Factors

  • Osteotoxicology: We coined this field to study the deleterious effects of environmental pollutants (microcystins, particulate matter, and microplastics, etc.) on bone health via immune dysregulation (Environ. Pollution, 2018).

 

  • Osteofertility: We coined this field & discovered that high salt diets impair both bone and male fertility through immune-bone-testis crosstalk (Scientific Reports, 2018; Reprod. Sci., 2023).

 

  • Stress & Osteoporosis: Using the UCMS model, we are dissecting how stress-induced gut dysbiosis and neuro-immune modulations disrupt Bone Health, i.e. “Brain-Gut-Immune-Bone axis”.

VI. Expanding Horizons

  • Osteoarthritis & Fractures: Investigating immune and gut metabolite contributions to cartilage and fracture healing. 

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  • Osteosarcoma: Linking tumour immunometabolism, gut metabolites, and CD8T/NK cell function in osteosarcoma progression (Bone Reports, 2024)

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  • Microgravity & Bone Health: Exploring its role in bone health. 

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  • Infections & Bone Health (COVID-19, ARDS & Sepsis): Evaluating microbiota-based prophylaxis against cytokine storms and their long-term skeletal implications (International Reviews of Immunology, 2021; Frontiers in Bioscience, 2021; Exploration in Immunology, 2023; Inflammation Research, 2023; Clinical Immunology, 2024).

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  • AI, ML & Bone Health: Applying machine learning to integrate osteo-omics datasets and design personalised immunotherapies for osteoporosis.

COLLABORATIONS

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© 2024,  Rupesh

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