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In the current study, we examined the regulation of TGF\u03b21 and the effects of TGF\u03b21 deletion on cellular response in the uninjured adult brain and in the injured and regenerating facial motor nucleus. To avoid lethal autoimmune inflammation within 3 weeks after birth in TGF\u03b21-deficient mice, this study was performed on a T- and B-cell-deficient RAG2\u2212\/\u2212 background. Compared with wild-type siblings, homozygous deletion of TGF\u03b21 resulted in an extensive inflammatory response in otherwise uninjured brain parenchyma. Astrocytes increased in GFAP and CD44 immunoreactivity; microglia showed proliferative activity, expression of phagocytosis-associated markers [\u03b1X\u03b22, B7.2, and MHC1 (major histocompatibility complex type 1)], and reduced branching. Ultrastructural analysis revealed focal blockade of axonal transport, perinodal damming of axonal organelles, focal demyelination, and myelin debris in granule-rich, phagocytic microglia. After facial axotomy, absence of TGF\u03b21 led to a fourfold increase in neuronal cell death (52 vs 13%), decreased central axonal sprouting, and significant delay in functional recovery. It also interfered with the microglial response, resulting in a diminished expression of early activation markers [ICAM1 (intercellular adhesion molecule 1), \u03b16\u03b21, and \u03b1M\u03b22] and reduced proliferation. In line with axonal and glial findings in the otherwise uninjured CNS, absence of endogenous TGF\u03b21 also caused an \u223c10% reduction in the number of normal motoneurons, pointing to an ongoing and potent trophic role of this anti-inflammatory cytokine in the normal as well as in the injured brain.<\/jats:p>","DOI":"10.1523\/jneurosci.2255-07.2007","type":"journal-article","created":{"date-parts":[[2007,10,17]],"date-time":"2007-10-17T17:27:59Z","timestamp":1192642079000},"page":"11201-11213","source":"Crossref","is-referenced-by-count":98,"title":["Endogenous Transforming Growth Factor \u03b21 Suppresses Inflammation and Promotes Survival in Adult CNS"],"prefix":"10.1523","volume":"27","author":[{"given":"Milan","family":"Makwana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard 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