biostudies-literatureUnknown46(1)Luo YFundació Institució dels Centres de Recerca de CatalunyaType II interferon (IFN) immunity is crucial for controlling intramacrophagic infections, driven by the interaction between innate immunity (macrophage-derived IL-12) and adaptive immunity (Th-derived IFN-γ). This study examines the maturation of type II IFN immunity in 55 healthy children (ages 1-18) to enable proper identification of deficiencies as part of the diagnostic evaluation of Mendelian Susceptibility to Mycobacterial Diseases (MSMD). The IL-12/IFN-γ axis was assessed through: (1) cytokine production after mycobacterial stimulation (Luminex and ELISA for IFN-γ, IL-12p70, TNF, CXCL10, IL-1RA, IL-10, IL-1β and IL-6), (2) IFN-γR1/R2 expression on monocytes, and (3) STAT1 phosphorylation/dephosphorylation. T cell maturation (primary IFN-γ source) was evaluated via immunophenotyping (naïve/memory/activated, Th1; Th2; Th17; Th1/17; Tfh) and proliferation assays. Main findings: (1) stable expression/production of key components of the IL-12/IFN-γ axis (IFN-γ, IL-12, TNF, IFN-γR1/2, and STAT1 activity) across ages confirming the stability of innate immune function throughout childhood; (2) increasing responses to IFN-γ with age reflected by increased CXCL10 production, and increase in the IFN-γ counter-acting anti-inflammatory cytokines (IL-10, IL-1RA); and (3) progressive T cell maturation, including Th1, Th17 and Th1/17 subsets, with significant milestones between 6 and 8.6 years, while T cell proliferative capacity remained stable. These observations highlight the stability of IL-12/IFN-γ axis innate components with age, accompanied by enhanced downstream IFN-γ signaling, aligning with the maturation of Th cell compartment. These underscore the limited benefit of age-specific controls in the evaluation of IL-12/IFN-γ axis in MSMD diagnosis, while emphasizing the importance of T cell maturation in the overall type II IFN immunity.Journal of clinical immunology13https://www.ebi.ac.uk/biostudies/studies/S-EPMC12831799biostudies-literatureAge-Related Patterns of Type II Interferon Immunity: Implications for Intramacrophagic Infections and MSMD Diagnosis During Childhood.PMC12831799Marquez JJuan MAcevedo DAlsina LCodina APeiro SMarti-Castellote CBolano VJou CFreixedas AEsteve-Sole ADeya-Martinez ALuo YGarcia-Garcia AArguello GVlagea AfalseAge-Related Patterns of Type II Interferon Immunity: Implications for Intramacrophagic Infections and MSMD Diagnosis During Childhood.Type II interferon (IFN) immunity is crucial for controlling intramacrophagic infections, driven by the interaction between innate immunity (macrophage-derived IL-12) and adaptive immunity (Th-derived IFN-γ). This study examines the maturation of type II IFN immunity in 55 healthy children (ages 1-18) to enable proper identification of deficiencies as part of the diagnostic evaluation of Mendelian Susceptibility to Mycobacterial Diseases (MSMD). The IL-12/IFN-γ axis was assessed through: (1) cytokine production after mycobacterial stimulation (Luminex and ELISA for IFN-γ, IL-12p70, TNF, CXCL10, IL-1RA, IL-10, IL-1β and IL-6), (2) IFN-γR1/R2 expression on monocytes, and (3) STAT1 phosphorylation/dephosphorylation. T cell maturation (primary IFN-γ source) was evaluated via immunophenotyping (naïve/memory/activated, Th1; Th2; Th17; Th1/17; Tfh) and proliferation assays. Main findings: (1) stable expression/production of key components of the IL-12/IFN-γ axis (IFN-γ, IL-12, TNF, IFN-γR1/2, and STAT1 activity) across ages confirming the stability of innate immune function throughout childhood; (2) increasing responses to IFN-γ with age reflected by increased CXCL10 production, and increase in the IFN-γ counter-acting anti-inflammatory cytokines (IL-10, IL-1RA); and (3) progressive T cell maturation, including Th1, Th17 and Th1/17 subsets, with significant milestones between 6 and 8.6 years, while T cell proliferative capacity remained stable. These observations highlight the stability of IL-12/IFN-γ axis innate components with age, accompanied by enhanced downstream IFN-γ signaling, aligning with the maturation of Th cell compartment. These underscore the limited benefit of age-specific controls in the evaluation of IL-12/IFN-γ axis in MSMD diagnosis, while emphasizing the importance of T cell maturation in the overall type II IFN immunity.2025-01-01T00:00:00Z2025 Dec2026-06-06T22:26:17.085Z2026-06-06T03:07:55.973ZS-EPMC128317994145243210.1007/s10875-025-01955-2